Showing posts with label Cancer. Show all posts
Showing posts with label Cancer. Show all posts

Alimta regimen didn't meet goal in study

Eli Lilly and Co. said Thursday a drug regimen including its Alimta therapy did not improve the survival of lung cancer patients in a late-stage clinical trial.

Lilly said patients who were treated with a combination of Alimta, Avastin, and the chemotherapy drug carboplatin lived for 12.6 months after the start of treatment. Patients who were treated with chemotherapy and Avastin, a drug that is made by Roche, had median survival of 13.4 months. There was not a statistically significant difference between the results of the two regimens.


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Blood test helps target Roche/OSI lung cancer drug


Testing for specific cancer protein markers in lung cancer patients' blood helps find those more likely to respond to Tarceva, a drug sold by Roche and OSI Pharmaceuticals , data showed on Friday.

A study presented at the European Lung Cancer Conference in Geneva showed that a relatively simple blood analysis known as a proteomic test can identify patients whose tumours are likely to shrink with the drug -- one of a class called EGFR-blockers.

"The bottom line is that the proteomic test -- comparing 'good' and 'poor' profiles -- was strongly prognostic," David Carbone from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, who led the study, said in a statement.

"Proteomics 'good' patients also had a significantly higher response rate than proteomics 'poor' patients."

Tarceva, known generically as erlotinib, is sold by OSI and Roche and is designed to block EGFR, a gene that is overactive in many types of cancer cells.

Other drugs in the same class include AstraZeneca's lung cancer medicine Iressa, and colon cancer drugs Vectibix from Amgen and Erbitux -- sold by Bristol-Myers Squibb , Eli Lilly and Merck KGaA .

Lung cancer is the biggest cancer killer around the world, killing 1.2 million people a year. Only 15 percent of people diagnosed with lung cancer are still alive five years later.

Patients can already be tested to see if they have the right type of genetic profile to respond well to EGFR-blocking drugs, but the methods involve gene sequencing, which is complex and expensive, or a technique called fluorescence in-situ hybridization (FISH), which requires a sample of tumour tissue.

Carbone said FISH was a better predictor of benefit for Tarceva, but noted it can only be done with enough of a tissue sample.

In this study, tumour samples were only available in 22 percent of patients, he said, while 99 percent of patients were able to be successfully assessed with the proteomic test. "This (proteomic) test ... may be of particular value for those in whom tumour tissue is inadequate or unavailable," Carbone said.


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A new drug target in lung cancer


Lung cancer patients whose tumors over-express a cell surface molecule called CXCR4 do significantly worse than those who do not, Canadian researchers have found. Their work, reported at the 2nd European Lung Cancer Conference in Geneva, highlights the exciting possibility that the molecule could soon become a new target for personalized cancer therapy.

CXCR4 is a receptor that is found on the surface of many different cell types in the body. It plays a role in immune system signaling between cells.

In cancer, evidence that CXCR4 is involved in the growth of tumors and their spreading throughout the body (metastasis) has been growing in recent years. For example, researchers have shown in studies in mice that blocking the action of CXCR4 inhibits metastasis. But its precise role in determining outcome and metastatic tendency, especially in lung cancer, is incompletely investigated.

Dr Gwyn Bebb and colleagues from the Tom Baker Cancer Centre in Calgary, Canada set out to explore whether patients whose tumors expressed high levels of the receptor had a worse prognosis than other lung cancer patients.

They studied tumor samples from 103 patients from the Glans-Look lung cancer database who were diagnosed with stage IV non-small-cell lung cancer (cancer which had already spread to other parts of the body) between 2003 and 2006. They found that 10.7% of the tumors over-expressed CXCR4. Those over-expressers had a significantly worse clinical outcome, with a median overall survival of 2.7 months, compared to 6.1 months among low-expressers.

If confirmed in an expanded series of 170 patients from the Glans-Look database, these results will suggest that new strategies to block CXCR4 should be tested in patients whose cancers over-express the molecule, the researchers say.

"I am quite excited about the possibility of using CXCR4 as a therapeutic target, but we need to learn more about its role in each specific malignancy," Dr Bebb said.

This possibility is especially promising because CXCR4 has been well studied in the context of HIV, where it is known to be a portal for the virus's entry into immune system cells. Drugs that block CXCR4 have already been developed for HIV/AIDS patients, and Dr Bebb's group thinks these drugs could quickly and easily be tested in the cancer setting.

"This is an exciting possibility," Dr Bebb said. "It seems very likely that a better understanding of the role of CXCR4 in lung cancer will lead to new treatment strategies and might allow us to meaningfully improve treatment for some lung cancer patients in the very near future."


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New Data on Two Nano-Scale Delivery Platforms


Celator Pharmaceuticals today announced data from animal studies demonstrating the superior bone marrow uptake of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection, its lead clinical-stage program, as well as the enhanced circulation kinetics and efficacy of its preclinical hydrophobic docetaxel prodrug nanoparticle (HDPN) formulation were presented at the 101st Annual Meeting of the American Association for Cancer Research in Washington, DC.

"This research continues to expand our understanding of the activity and potential clinical benefits of improved cancer therapeutics based on our proprietary technologies; the CombiPlex® platform and the nanoparticle prodrug delivery platform," said Scott Jackson, chief executive officer of Celator Pharmaceuticals. "The work done with CPX-351 helps explain the encouraging anti-leukemic activity we are seeing in Phase 2 clinical studies and the results seen with HDPN contributed to this product being selected for study by the NCI's Nanotechnology Characterization Laboratory."

In the first presentation, researchers reported on the circulation characteristics and anti-tumor activity of HDPN in mice bearing HT-29 human colorectal tumor xenografts. Two nanoparticle preparations of the docetaxel pro-drug demonstrated significantly greater plasma half-lives than docetaxel formulated in polysorbate 80, the detergent drug solubilizer used in the marketed product Taxotere®. Furthermore, when administered at either their respective maximum tolerated doses or at equimolar doses to free docetaxel, the two HDPN preparations produced greater antitumor activity, as measured by tumor growth delay, than the free docetaxel. These results confirmed that the proprietary HDPN approach -- encapsulating hydrophobic docetaxel prodrugs in block co-polymer nanoparticles -- produces prolonged circulation kinetics and enhanced therapeutic activity. HDPN is currently undergoing comprehensive pre-clinical evaluation at the National Cancer Institute's (NCI) Nanotechnology Characterization Laboratory to support an eventual investigational new drug (IND) filing with the U.S. Food and Drug Administration.

The second presentation described results of a biodistribution comparison of CPX-351 to empty liposomes in a human leukemia xenograft model. The plasma clearance of both CPX-351 and the empty liposomes was similar in both leukemic and non-leukemic mice and both formulations had similar organ distribution profiles. However, accumulation of CPX-351 in bone marrow was 20 to 50 percent higher than that of the empty liposomes in cancer-free mice and 75 percent higher in leukemic mice after the first injection. CPX-351 accumulation increased an additional 20 percent with subsequent injections. The researchers concluded that the presence of encapsulated cytarabine:daunorubicin in CPX-351 markedly augmented marrow uptake and/or retention of the liposomes, a benefit that along with the prolonged circulation made possible by liposomal encapsulation itself, helps increase the exposure of tumor cells to the two active drugs at the synergistic ratio.



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Tamoxifen, raloxifene cut breast cancer risk in half


Women at high risk can take either drug as preventive therapy, researchers in a seven-year study say.

Two drugs taken by women at high risk for breast cancer — tamoxifen and raloxifene — both reduce the risk of the disease by about 50% in high-risk post-menopausal women while they are taking the medications, researchers said Monday. The benefits of raloxifene fall off more quickly once women stop taking them, however, and the increased benefits of tamoxifen come at a price: a higher risk of uterine cancer, blood clots and cataracts — although the absolute risks of all three remain low.

"These are relatively inexpensive drugs that reduce breast cancer by about 50% with side effects that are modest," said Dr. Gabriel N. Hortobagyi of the University of Texas M.D. Anderson Cancer Center in Houston, one of the researchers. "We need to reassess why we are not using these drugs more broadly," he said at a news conference at a meeting of the American Assn. of Cancer Research, where the results were presented.

The new results represent an extension of a clinical trial that was first reported in 2007 and allow refinement of the researchers' earlier conclusions. But the basic message is that women can confidently take either drug to sharply reduce their risk of dying from breast cancer.

"If they can't tolerate their first choice, they can take advantage of the second drug," said Dr. Larry Wickerham of Allegheny General Hospital in Pittsburgh, another researcher on the team.

The trial enrolled 19,747 post-menopausal women over the age of 35 who had an above-normal risk of breast cancer because they had breast cancer genes or a family history of the disease. While the average 60- to 64-year-old woman has about a 1.66% risk of developing breast cancer over a five-year period, the women in the study averaged twice that risk, and some had an even higher risk. (Women can calculate their own risk at http://www.cancer.gov/bcrisktool).

Women who had uncontrolled diabetes or hypertension were excluded from the trial, as were those at a high risk for stroke or blood clots.

The women were given either tamoxifen (brand name Nolvadex, also available generically) or raloxifene (brand name Evista) daily for five years.

The initial results released after the end of that five years showed that both drugs reduced the risk of breast cancer by 50%. Based on those findings, the Food and Drug Administration approved the use of raloxifene to prevent breast cancer in high-risk post-menopausal women. Tamoxifen was already approved in both pre- and post-menopausal high-risk women.

The new report, which provides an additional 21 months of follow-up, shows that the benefits of tamoxifen continued after the women stopped taking it, but those of raloxifene fell off quickly. Over the nearly seven years of the study, tamoxifen reduced risk by 50%, but raloxifene reduced it by only 38%. That translates to 247 cases of invasive breast cancer (tumors that are likely to spread beyond the breast) among 9,736 women who took tamoxifen and 310 cases in the 9,754 women who took raloxifene.

Previous studies have shown that tamoxifen provides protection for at least seven to 10 years after women stop taking the drug.

About half the women in the trial had previously had hysterectomies and were not at risk of uterine cancer. Among the rest, 65 of 4,739 women in the tamoxifen group developed uterine cancer, compared with 37 of the 4,717 in the raloxifene group.

The raloxifene group also had 28% fewer blood clots in a major vein and 20% fewer blood clots in the lungs, but the absolute number of events was low in both groups.

The fact that raloxifene has fewer side effects may induce more women to adopt preventive therapy, said Dr. Jack Jacoub, an oncologist at Memorial Care Cancer Institute at Orange Coast Memorial Medical Center in Fountain Valley, who was not involved in the research.

In the United States, "we have actually had difficulty getting women to accept preventive measures for breast cancer, and the primary deterrent has been the toxicity" of tamoxifen, Jacoub said. If these results are presented to women properly, "I think we will see more women receiving this therapy."

The study was funded by the National Cancer Institute, which provides more information about the results at http://www.cancer.gov/newscenter/STARresultsQandA.


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Cancer Drug Seems to Work by Activating Virus


The cancer drug cyclophosphamide activates a viral infection that helps anti-viral medications eliminate a virus-linked cancer, says a new study.

The drug is used to treat Burkitt lymphoma, an aggressive, fast-growing type of non-Hodgkin lymphoma that often occurs in children. In Africa, the cancer is caused by the Epstein-Barr virus (EBV), which typically remains dormant inside tumor cells.

This study of 21 patients, ages 5 to 15, who were being treated with cyclophosphamide, found that the drug triggers an active EBV infection. Increased replication of the virus in cancer cells makes the cells more susceptible to antiviral drugs, which kill cells containing the replicating virus.

The study was published in the April issue of the journal Clinical Cancer Research.

"What we have learned from this work is a potential means of capitalizing on presence of viral genomes within tumor cells to alter those tumor cells in a way that makes them more susceptible to treatment. Our findings have implications for other EBV-related malignancies that, overall, are among the most common cancers worldwide," Dr. Margaret Gulley, a professor of pathology and laboratory medicine at the University of North Carolina at Chapel Hill School of Medicine, said in a news release.

EBV infects more than 90 percent of people worldwide and is associated with a number of diseases including lymphomas, gastric cancer, and nose and throat cancer.

The next step in this research is a clinical trial to test the use of a cancer drug and an antiviral drug simultaneously, Gulley said.


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Clinical Trial of Experimental Mesothelioma Drug Promising


Researchers announced positive results from tests of an experimental anti-cancer drug known as NGR-hTNF in controlling the cancer of patients with malignant pleural mesothelioma. Mesothelioma is an incurable cancer of the lining of the lung associated with asbestos exposure.

NGR-hTNF is a novel drug compound that includes a peptide—a chain of amino acids—that homes in on cancer cells—and a type of protein known as tumor necrosis factor that helps regulate the immune system response to cancerous tumors. Developed by an Italian pharmaceutical company, MolMed S.p.A., the drug is designed to better permeate cancerous tumors and act directly on blood vessels that feed a tumor’s growth.

In an article published this week in the Journal of Clinical Oncology, Italian researchers said NGR-hTNF was given to 57 mesothelioma patients either every three weeks or every week. The patients had previously undergone chemotherapy and had a relapse. The results showed the drug temporarily stopped the advance of the cancer in 26 patients for about five months on average. Median survival was 12 months.

The researchers said the disease control provided by NGR-hTNF and patients’ ability to tolerate the drug warranted further study with patients with advanced pleural mesothelioma.

The drug is being studied as an alternative treatment for patients whose cancer is not responding to the more standard chemotherapy regimen involving permetrexed. A phase III clinical study is underway. Researchers are exploring it use by itself or in combination with other medications.

On the basis of the latest results, the drug was granted orphan drug designation for treatment of malignant mesothelioma in the United State and in Europe, MolMed S.p.A., announced.

The federal Orphan Drug Act provides special status to drugs used to treat a rare disease or condition at the request of the drug sponsor. MolMed S.p.A., an Italian pharmaceutical company, is developing the drug. The orphan designation provides tax credits and government incentives to sponsors that bring develop drugs to treat rare diseases. About 2,000 to 3,000 people die of mesothelioma in the United States each year, but incidence of the disease has increased significantly in recent decades.

The drug must go through the Food and Drug Administration marketing approval process like any other drug. Orphan drugs often receive expedited review because they are for serious or life threatening diseases, according to the Food and Drug Administration.


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FDA Approves Azaya Therapeutics Investigational New Drug Application

Azaya Therapeutics, Inc. announced today that the Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for its lead product "ATI-1123," a novel and improved formulation of Taxotere® (docetaxel), a leading chemotherapy drug with worldwide annual sales of over $2.8 billion.

Azaya’s Phase I clinical study will now open for enrollment at two premier cancer research centers in Texas: South Texas Accelerated Research Therapeutics at the START Center for Cancer Care in San Antonio and The Mary Crowley Cancer Research Center in Dallas. Patients with solid tumors that have not responded to treatment with other anti-cancer agents will be enrolled in the study. The study is designed as an open-label, dose-escalation study that will determine the safety, tolerability and pharmacokinetics of the drug. The study also provides for the collection of efficacy data.

"The FDA’s acceptance of our IND package is an important milestone in the commercialization of this important and innovative new cancer treatment," said Michael T. Dwyer, president and CEO of Azaya. "Developing a cancer treatment such as ours takes an extraordinary amount of time and effort, and I am pleased to initiate our Phase I trial for patient enrollment," he added.

Azaya utilizes a proprietary manufacturing process to produce liposome-encapsulated chemotherapeutics that eliminates the use of toxic carriers and incorporates a naturally occurring protein to stabilize the liposomal encapsulated drug. Preclinical studies have demonstrated improvement in the toxicology profile and an enhanced efficacy of ATI-1123 compared to Taxotere® in a number of tumor models.

Azaya Therapeutics is a San Antonio-based emerging pharmaceutical company whose innovative technology platform makes safer and more effective cancer treatments. Its unique and proprietary Protein Stabilized Nanoparticle (PSN™) platform addresses the significant problems associated with delivery of water insoluble drugs. Azaya has leveraged this platform to develop differentiated drug products for the global oncology market. The company’s management is highly experienced in biotechnology and oncology and has a track record of obtaining FDA drug approvals and successfully building companies.



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Drugs to treat anemia in cancer patients linked to thromboembolism

Medications frequently given to cancer patients to reduce their risk of anemia are associated with an increased risk of deep vein thrombosis or pulmonary embolism, according to new research led by Dawn Hershman, M.D, M.S., co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center. The findings will be published online on Nov. 10, 2009 in the Journal of the National Cancer Institute .

The anemia-reducing medications, known as erythropoiesis-stimulating agents (i.e., erythropoietin and darbopoietin) or ESAs, stimulate red blood cell production and are intended to reduce the number of blood transfusions required during chemotherapy. However, concerns about the risks of deep vein thrombosis or pulmonary embolism (manifestations of venous thromboembolism) and mortality exist.

"This research answers important questions about outcomes of ESAs when used in long-term clinical practice with oncology patients," said Dr. Hershman, the Florence Irving Assistant Professor of Medicine and Epidemiology at Columbia University Medical Center, whose research is dedicated to examining cancer survivorship. "While ESAs were given to reduce the need for blood transfusions, a substantial reduction in the use of blood transfusions was not observed. However, an increase risk of deep vein thrombosis or pulmonary embolism was confirmed."

"This analysis confirms the association between ESAs and venous thromboembolism, which was observed in previous meta-analysis," said Dr. Hershman. "This new finding is significant because where the meta-analysis looked at pooled data from randomized clinical trials, this data is from community practice -- real-life clinical settings -- where you can often see things that wouldn't necessarily show-up in a short-term, 12-week study. Additionally, this analysis included data from more than 50,000 patients? including those with more advanced cancer or high-risk status, who therefore might not have been candidates for clinical trials."

Based on previous findings, in the spring of 2007, the FDA required a black-box warning on ESAs about the potential for venous thromboembolism, tumor promotion, and decreased survival in ESA users. The warning suggested limiting the use of ESAs to specific tumor types, durations, doses, and targeted hemoglobin levels. In addition, the Center for Medicare and Medicaid Services proposed eliminating or limiting coverage for ESAs as treatment for some cancers.

"But what is reassuring about our findings are that they don't show an increased risk of mortality when ESAs are given with chemotherapy," said Dr. Hershman.

Dr. Hershman and colleagues analyzed the association between use of ESAs and venous thromboembolism and overall survival in patients who were 65 years or older and diagnosed with colon, non-small cell lung, or breast cancer or diffuse large B-cell lymphoma, between 1991-2002. These cancers were chosen because they were thought to be common cancers for which ESAs were frequently used. Patients were identified in the Surveillance, Epidemiology, and End Results?Medicare database, which at the time contained records of patients diagnosed with cancer in regions that represented approximately 14 percent of the U.S. population.

Results demonstrated that more patients who received an ESA developed deep vein thrombosis or pulmonary embolism, as compared to patients who did not. Overall survival was similar in both groups. The number of patients receiving ESAs increased approximately 10-fold from 1991 through 2002, with approximately 50 percent of patients with advanced cancer undergoing chemotherapy receiving ESAs by 2002. The rate of blood transfusion per year during the same time period, however, remained constant at 22 percent.

"Further efforts at monitoring use and long-term toxicity of expensive oncology drugs should be put in place to ensure that for any drug the benefits outweigh the risks in community practice," the authors write in the paper.

In the JNCI paper, the authors note that ESAs may be of particular interest from a public policy perspective because of the costs associated with their use. Total U.S. sales of ESAs were $10 billion in 2006, accounting for a greater Medicare Part B expenditure than any other drug.

The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became a National Cancer Institute (NCI)?designated comprehensive cancer center in 1979. The designation recognizes the Center's collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer.


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New vasculitis therapy may help patients keep infertility, cancer at bay

A drug previously approved for the treatment of non-Hodgkin’s B cell lymphoma and rheumatoid arthritis, can treat severe ANCA-associated vasculitis as effectively as cyclophosphamide, the current standard therapy, say researchers.

The finding of Rituxan has been presented at the annual meeting of the American College of Rheumatology in Philadelphia.

“The reason this is a big deal is that this is a disease where people would come in and be told ‘listen, we are probably going to be able to get on top of your life-threatening disease by using cyclophosphamide, there is the potential for major side effects down the road from this drug,’” said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery in New York.

“This study provides strong evidence that Rituxan works as well as cyclophosphamide, at least in terms of getting patients into remission, and over that acute hump of being very ill. And, we can treat patients without the likelihood of causing infertility or causing secondary cancers, which have been a concern with the use of cyclophosphamide,” the expert added.

Hospital for Special Surgery was one of nine centers involved in the Phase III trial, which was led by Ulrich Specks, M.D., a professor of medicine in the Department of Pulmonary and Critical Care Medicine at the Mayo Clinic, and John Stone, M.D., MPH, director, Clinical Rheumatology, Massachusetts General Hospital.

Vasculitis, an inflammation of the blood vessels, can damage tissues and organs and, in severe cases, lead to death. Specifically, the study examined something known as ANCA-associated vasculitis that includes Wegener’s granulomatosis and microscopic polyangiitis.

“The reason this is such a significant study is that this is an uncommon but devastating group of diseases,” said Dr. Spiera.

Prior to the use of cyclophosphamide treatment, 70 percent of patients who were diagnosed with severe forms of ANCA-associated vasculitis could be expected to be dead within three years. In the 1970s, doctors discovered that cyclophosphamide was extremely effective at combating the disease and could put people into remission. In the ensuing decades, however, doctors recognized that these drugs came with a price.

“If you followed patients long enough, you found they had a higher risk of leukemias, lymphomas and solid tumors,” said Dr. Spiera, who is also an Associate Professor at Weill Cornell Medical College. “People would sometimes develop terrible infections. Women, almost reliably, would become infertile, as did many men. So, although it was a dramatically effective drug at reducing remissions in these patients, it came at a price.”

In the current study, nine centers enrolled a total of 197 patients with severe Wegener’s granulomatosis or microscopic polyangiitis, two of the more common types of ANCA-associated vasculitis. Patients were given steroids and randomized to receive either the standard treatment with cyclophosphamide or Rituxan given at a dose of 375 mg/m2 weekly for four weeks.

At the time of the data analysis, 84 of the 99 patients in the Rituxan arm and 81 of the 98 patients in the cyclophosphamide arm had completed six months of follow-up. Investigators found that the treatments were equally effective in putting patients into remission and that, in fact, the treatment outcomes looked slightly better in patients receiving Rituxan.

“These results show that the Rituxan worked at least as well as cyclophosphamide,” Dr. Spiera said. “If anything, there was almost a hint of it maybe looking a little better, and even in the short term, it looked safer in some respects. This study shows that there is strong evidence that Rituxan may be an alternative to cyclophosphamide in this disease. It might help manage flares in patients who have gone into remission, and it could be a consideration as first-line therapy, especially in women of child bearing potential who have a good chance of losing their fertility if treated with cyclophosphamide.”



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New Drug Aims To 'Seek And Destroy' Many Types Of Cancer

A new drug designed to “seek and destroy” common cancers such as breast, prostate, endometrial, pancreatic, ovarian, skin and testicular cancers is being tested at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare.

The Phase 1 clinical trial will help determine if EP-100 is safe and effective for use among patients with solid cancer tumors, with fewer side effects than chemotherapy or radiation treatment.

TCRS is a partnership of the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare. The partnership allows molecular and genomic discoveries made by TGen and others around the world to reach the patient bedside in the Virginia G. Piper Cancer Center at Scottsdale Healthcare as quickly as possible through clinical trials with agents directed at specific targets in patients’ tumors.

According to Ramesh K. Ramanathan, MD, principal investigator for the trial in Scottsdale, the drug is a membrane-disrupting peptide (tMDP) designed to “seek and destroy” cancer cells by targeting those with excessive luteinizing hormone releasing hormone (LHRH) receptors.

Excessive LHRH receptors are found in a wide range of cancers, including breast, prostate, endometrial, pancreatic, ovarian, skin and testicular cancers.

Mike Janicek, MD, a Gynecologist Oncologist who practices at the Virginia G. Piper Cancer Center at Scottsdale Healthcare said, “I am looking forward to participating in the study with EP100, especially for ovarian and uterine cancer patients. Often patients with advanced cancer will need new therapies and a targeted treatment like EP100 is the next frontier of research.”

The study is designed to evaluate the safety of EP100 and will enroll as many as 36 adult patients with solid tumors whose tumor biopsies indicate that they have excessive LHRH receptors.

EP-100 will be administered intravenously for three out of four weeks. Once the maximum tolerated dose has been established, additional subjects with specific diagnoses of either breast, ovarian, endometrial, pancreatic or prostate cancer will be enrolled. EP-100 is produced by Esperance Pharmaceuticals of Baton Rouge, La., and was culled from a range of drugs tested at TGen Drug Development Services (TD2) in Scottsdale.

“It brings with it a killer, a toxin. It’s a way of targeting a toxin to the cancer tumor cells,’’ said Dr. Steve Gately, president and chief scientific advisor at TD2. “Our goal would be to find that set of patients who are highly responsive; who have the greatest benefit. We’d like to accelerate the government approval for that agent.’’

The clinical trials could show that EP-100 is effective with certain types of cancer, Dr. Gately said. “Perhaps there is a genetic context under which certain patients may be more responsive. We want to find those patients.’’

Dr. Hector Alila, president of Esperance, said EP-100 has the potential to offer an improved safety and effectiveness over existing therapies, such as radiation or chemotherapy.

“Preclinical studies of EP-100 demonstrated this candidate’s efficacy across multiple indications in oncology, including aggressive cancers known to be resistant to the current standards of care and, importantly, studies of EP-100’s mechanism-of-action support that it targets and selectively kills cancer cells without harming normal cells,” Dr. Alila said.



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Metals could forge new cancer drug

Drugs made using unusual metals could form an effective treatment against colon and ovarian cancer, including cancerous cells that have developed immunity to other drugs, according to research at the University of Warwick and the University of Leeds.

The study, published in the Journal of Medicinal Chemistry, showed that a range of compounds containing the two transition metals Ruthenium and Osmium, which are found in the same part of the periodic table as precious metals like platinum and gold, cause significant cell death in ovarian and colon cancer cells.

The compounds were also effective against ovarian cancer cells which are resistant to the drug Cisplatin, the most successful transition metal drug, which contains the metal platinum.

Dr Patrick McGowan, one of the lead authors of the research from the School of Chemistry at the University of Leeds, explains: "Ruthenium and Osmium compounds are showing very high levels of activity against ovarian cancer, which is a significant step forward in the field of medicinal chemistry.

Sabine H. van Rijt, lead researcher in the laboratory of Professor Peter Sadler in the Department of Chemistry at the University of Warwick, said:

"Most interestingly, cancerous cells that have shown resistance to the most successful transition metal drug, Cisplatin, show a high death rate with these new compounds."

Professor Sadler, at the University of Warwick, commented that he is "excited by the novel design features in these compounds which might enable activity to be switched on and off".

Cisplatin was discovered in the 1970s and is one of the most effective cancer drugs on the market, with a 95% cure rate against testicular cancer. Since the success of Cisplatin, chemists all over the world have been trying to discover whether other transition metal compounds can be used to treat cancer.

In this type of anti cancer drug transition metal atoms bind to DNA molecules which trigger apoptosis, or programmed cell death, in the cancerous cells.

The study is a collaboration between the universities of Warwick and Leeds and was funded by the Engineering and Physical Sciences Research Council (EPSRC).



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Spectrum says FDA refuses to OK new plea on cancer drug

Spectrum Pharmaceuticals said U.S. health regulators declined to approve its supplementary marketing application for its advanced metastatic colorectal cancer drug Fusilev in its current form, sending its shares down 22 percent.

Spectrum said the U.S. Food and Drug Administration (FDA) noted that the submission did not show that Fusilev is non-inferior to standard treatment leucovorin, and it did not request any changes to the currently approved indications.

Spectrum, which received a label expansion approval for another cancer drug last month, said it plans to request a meeting with the FDA to discuss options for the approval of Fusilev.

"There is going to be a delay (in Fusilev approval) and it wasn't really expected," said Morgan Joseph & Co analyst Shiv Kapoor, who in September downgraded Spectrum shares to "hold" from "buy."

Kapoor said he would wait for Spectrum to meet the FDA and determine the next step needed for the approval of the drug.

"The question really here would be, will this be a meaningful delay or not," he said.

Fusilev is currently approved by the FDA as a rescue after high dose of methotrexate therapy in patients with osteosarcoma, a type of bone cancer.

The drug is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonist, a type of chemotherapy.

Spectrum shares were down 17 percent at $5.17 in late morning trade on Friday. They touched a low of $4.82 earlier in the session, making them one of the top percentage losers on Nasdaq.



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GenSpera Receives FDA Approval for G-202 Phase I Cancer Trial

GenSpera, Inc. announced today that the Food and Drug Administration (FDA) has
approved its Investigational New Drug (IND) application to begin a Phase I study
with its target activated pro-drug, G-202, for the treatment of cancer.

GenSpera`s Phase I clinical study is anticipated to begin in the fourth quarter of 2009 at two major cancer centers: the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, in Baltimore, MD, and the University of Wisconsin Carbone Cancer Center, in Madison, WI. The study is designed to enroll patients with cancers that have progressed after treatment with other anti-cancer agents. The primary endpoints of the open-label, dose-escalation study will be to determine the safety, tolerability and pharmacokinetics of the drug, although
the design allows the collection of efficacy data as well.

"The acceptance of our IND by the FDA constitutes a defining milestone in the development of an entirely new class of anti-cancer agent that is expected to have broad utility across many tumor types," commented Dr. Craig Dionne, GenSpera CEO. "We are also pleased that this event underscores the company`s drug development capabilities and commitment to timely achievement of important corporate milestones."

G-202 is a pro-drug that is selectively activated within tumors by an enzyme present on the tumor blood vessels. In preclinical testing, G-202 was shown to ablate tumors in animal models of breast cancer, prostate cancer and kidney cancer. GenSpera, Inc. owns and controls all rights to G-202 and anticipates a strategic partnership to maximize the value of the drug as it progresses through future clinical trials.

About GenSpera

GenSpera, Inc. is a development stage oncology company focused on therapeutics which deliver a potent, unique and patented drug directly to tumors. GenSpera`s technology platform combines a potent cytotoxin (12ADT) with a pro-drug delivery system that activates the drug only within the tumor. Unlike standard cancer drugs, plant-derived 12ADT kills cells independent of their division rate, thus making it effective at killing all fast- and slow- growing cancers and cancer stem cells. GenSpera`s pro-drug platform is the subject of six issued patents
with six additional patents pending.

GenSpera plans to initiate a Phase I cancer trial with its lead drug, G-202, in the fourth quarter of 2009. G-202 targets the established blood vessels that nourish solid tumors, thus destroying the tumor`s blood supply. This is a dramatic improvement upon anti-angiogenic drugs that primarily only stop the growth of new blood vessels. Upon completion of its Phase I trial, GenSpera expects to initiate multiple Phase II trials for G-202 in several different cancer types. The company`s second drug, G-115, will directly target prostate cancer.



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New Compound Fights Tumors

An experimental cancer drug that switches off the so-called "Hedgehog" pathway beat back tumors in more than half of patients with advanced basal cell carcinoma, a type of skin cancer.

The drug also helped a 26-year-old man suffering from medulloblastoma, the most common form of brain cancer in children.

"We were both pleased and surprised. We had hoped that we might see responses like this but we in no way anticipated that, within the context of a phase 1 clinical trial, we would see this level of anti-tumor activity," said Dr. Charles M. Rudin, who authored two papers on the findings that appear in the Sept. 2 online edition of the New England Journal of Medicine. "These are the first reports in the literature of any Hedgehog inhibitor being used clinically."

Phase 1 trials are conducted to look at a drug's safety profile and determine the right dose. Phase 2 and phase 3 trials typically look at effectiveness.

Also exciting, however, is the fact that the Hedgehog pathway has been implicated in other cancers, notably colon cancer and ovarian cancer, albeit in a different way.

Researchers are going forward to look at the potential of the molecule, known as GDC-0449, to treat these types of cancers as a one-drug regimen, and in combination with other drugs for other solid tumor malignancies, said Rudin, who is associate director for clinical research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.

One expert noted that finding a compound that might control the Hedgehog pathway could have far-reaching implications.

"These are phase 1 trials so they're quite preliminary, but the drug is quite effective in at least a subset of the patients treated," said Dr. Andrzej Dlugosz, author of an accompanying editorial and a professor in the department of dermatology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor. "The reason we're so excited is that there are now a large number of cancers that have also been linked to abnormalities in this pathway, including pancreatic, colon, ovarian and prostate. It's quite an impressive list. The data is pretty strong suggesting that if you shut down the pathway, it can have a pretty profound effect on those tumor cells. If it can work in these cancers, maybe it can work in other cancers, even though the signaling there is more complex."

But another researcher warned that it is premature to get too excited about the results.

"It's great to see something with so much potential, but it really is potential," said Dr. Clifford Perlis, director of Mohs Micrographic Surgery and Dermatologic Surgery at Fox Chase Cancer Center in Philadelphia.

However, he added, "there are other companies developing Hedgehog inhibitors as well, so I think people should be paying attention to this."

The Hedgehog gene, so named because it was first discovered in flies with hair resembling the spikes of hedgehogs, "is really important during early embryonic development in pretty much all animal species from flies to mice to humans, and for pretty much every tissue you can imagine," explained Frederic de Sauvage, also an author on both papers. "But remarkably in adults, it seems to be mostly turned off."

De Sauvage is vice president of research, molecular biology, at Genentech, which developed the molecule and funded the study.

Some 1 million Americans get basal cell carcinoma each year. It often doesn't spread but, once it has, there are no approved treatments. Medulloblastoma is an aggressive form of brain tumor.

The first trial enrolled 33 individuals whose basal cell carcinoma had spread locally or to distant organs.

Half of the participants who had distant metastases saw a reduction in tumor size, as did 60 percent of those with locally advanced cancer. The rest had either stable or progressive disease after 10 months of follow-up.

But "stable" in this population may not mean much, Perlis pointed out, as it is generally a very slow-growing cancer.

The man with medulloblastoma also saw a significant shrinkage of his tumor, along with vastly improved quality of life, but only for two months. He later died.

A third study by some of the same authors, this one published online Sept. 2 in Science Express, discovered that treatment with GDC-0449 actually spurred another mutation in a gene called SMO, which caused the brain tumor to become resistant to the drug.

Because the Hedgehog pathway does not actually do much in adults, side effects were minimal, said de Sauvage.

GDC-0449 would likely be used very differently, depending on which type of cancer it is targeting.

In the case of basal cell carcinoma and medulloblastoma, the mutation in the Hedgehog pathway "really drives the formation of these tumors," de Sauvage said. "This molecule inhibits the pathway very specifically and, to date, we only know of these two types of tumor where the pathway is mutated." That means GDC-0449 is effective on its own.

But in colon and ovarian cancer, he continued, the pathway recruits surrounding cells to promote the cancer. In these types of tumors, GDC-0449 would have to be combined with other drugs.

Source : www.empowher.com


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New Cancer Drug Delivery System Is Effective and Reversible

The team of investigators, led by faculty members Li Yu, Ph.D., and Jianjun Cheng, Ph.D., M.S., who is also a member of the Siteman Center of Cancer Nanotechnology Excellence, began its work with the knowledge that small, membrane-bound compartments, called liposomes, are useful as drug-delivery vehicles. When linked to molecules that target receptors on cancer cells, liposomes can enter and dump their cancer-killing contents into those cells.

To target tumor cells, the investigators focused their efforts on a family of small molecules called aptamers. Aptamers are short strands of DNA or RNA; they are highly efficient at binding to biomolecules and are easy to make, label, and manipulate. Dr. Lu's laboratory specializes in isolating aptamers that bind to specific molecules and converting them into effective sensors and diagnostic agents. His team used an aptamer that binds to nucleolin receptors, which are found in abundance on certain breast cancer cells. The researchers then developed an effective method for attaching the aptamer to a liposome loaded with cisplatin, a drug that effectively kills cancer cells but has troublesome side effects when administered intravenously.

Tests in cells grown in the lab yielded promising results. Four days after the investigators exposed the cells to the new drug delivery system, 60% of the breast cancer cells had died, whereas less than 12% of breast cancer cells treated with cisplatin alone had died. "By labeling a liposome that contains cisplatin with a cancer cell-specific aptamer, we have shown delivery of the drugs to cancer cells without significant damage to regular cells," Dr. Lu said, "making it possible to maximize the drug potency while minimizing its side effects."

This approach "integrates the advantages of small molecules and antibodies," said Dr. Cheng, who helped pioneer the use of aptamers as targeting molecules for drug delivery. "This is the first study to integrate the aptamers and the liposome."

Another advantage of using aptamers as targeting agents is that they are easily disabled since they readily bind to complementary DNA (cDNA), which prevents them from interacting with cell receptors. In an additional set of experiments, the investigators showed that adding cDNA to cultured cells treated with the aptamer-targeted liposomes did in fact block all cell-killing activity of liposomal cisplatin.

"You can change aptamers to target a different type of cancer, you can change the therapeutic molecules to fight cancer or other diseases, and you can reverse the dose," Dr. Cheng said. "That's a lot of tools in the toolbox. It has great potential."

Source : www.nanotech-now.com


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New cancer drugs prove promising

Researchers of different Boston-area institutions recently discovered a chemical that worked in mice to kill aggressive cells within breast cancer cells that have the ability to form more cancerous cells.

The aggressive cancer cells, known as cancer stem cells, are thought to be the catalysts that cause cancers to grow and spread, and these are the cells that can reemerge after treatment. In general, cancer stem cells are largely resistant to current cancer therapies.

In an article by Broad Communications, Eric Lander, director of the Broad Institute of MIT and Harvard, and author of the findings published in the Aug. 13 advanced online issue of "Cell," said that there are many therapies that kill the bulk of a tumor only to see it grow anew.

"The holy grail of finding new cancer drugs would be to find something that would specifically kill cancer cells but not normal cells," Cynthia Moore, ISU associate professor of biological sciences, said.

It would seem then that the researchers have seen a glimmer of their holy grail. Eventually through the screening of 30 different promising chemicals, researchers identified one chemical, salinomycin, that killed cancer stem cells.

The compound was able to reduce the number of stem cells by more than 100-fold, and reduce breast tumor growth in mice. Now only more research will tell if the chemical will be fit for the use of humans.

"I think it would definitely give them more hope. People are looking for any new treatments," Julie Peterson, junior dance performance and elementary education major, said.

However, studying cancer stem cells was difficult as they are few and far between and do not grow well outside the body. This limited the amount available for analysis, slowing down research.

Researchers were finally able to beat this obstacle thanks to recent findings that suggested a way to generate in the laboratory large numbers of cells with stem cell-like qualities.

"We screen thousands and thousands of drugs. Most don’t show progress....We have the technology now to screen a lot of drugs simultaneously," Moore said.

While scientists seem to have found a better treatment for breast cancer, there still remain hundreds of different cancers.

Moore said, "One important point is that cancer includes more than 100 different diseases that are all cancers, but it is unlikely that the same drug will affect different cancers in the same way."

In fact, Moore felt prevention is a better way to go.

"If there was some way to prevent the initial cell from starting to divide and become a cancer that would be great. The problem is detection. Once it starts multiplying that first cell isn’t going to work for you. If you could stop that first cell from becoming cancer that would be perfect," Moore said.

However, Peterson said, "I think both are really important [prevention and new drugs]. Cancer is definitely a problem in our society so it’s good to find a cure."

Nevertheless, the Boston-area researchers continue their work in the hopes of developing a drug for humans. In an article by Broad Communications, Piyush Gupta, a researcher at the Broad Institute of MIT and Harvard, and co-author of the study said that their work revealed biological effects of targeting stem cells and moreover, it suggested a general approach to finding anti-cancer therapies that could be applied to any solid tumor maintained by cancer stem cells.

"It’s possible, but there is an awful lot we don’t know. If the answer was easy we would have figured it out a long time ago," Moore said.

Two different institutions conducted cancer stem cell research. The Whitehead Institute for Biomedical Research is a nonprofit, independent research and educational institution.

The Broad Institute of MIT and Harvard was founded to empower a new generation of creative scientists to transform medicine with new genome-based knowledge.

Source : www.dailyvidette.com


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Immunomedics Announces FDA Allowance of Investigational New Drug Application for Milatuzumab-Doxorubicin Conjugate

Immunomedics, Inc. , a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, today announced the allowance of an investigational new drug (IND) application filed with the U.S. Food and Drug Administration (FDA) to initiate a Phase I/II clinical trial of the doxorubicin conjugate of milatuzumab for the treatment of patients with multiple myeloma. This product candidate is the Company's first antibody-drug conjugate to enter human studies.

The primary objective of the open-label, multi-center study is to evaluate the safety and tolerability of the antibody-drug conjugate in patients with recurrent or refractory multiple myeloma. Preliminary information on efficacy, pharmacokinetics, and immunogenicity will also be obtained.

"Due to its rapidly internalizing nature when bound to the CD74 receptor, milatuzumab is an ideal antibody for the targeted delivery of chemotherapeutic agents, such as doxorubicin, to tumors expressing CD74, as indicated in several articles published by our scientists," commented Cynthia L. Sullivan, President and CEO. "We are pleased with the allowance and are eager to begin the clinical assessment of the antibody-drug conjugate, which has demonstrated very potent anti-tumor activities in preclinical studies," she added. Ms. Sullivan elaborated further: "Our chemists have developed some unique drug conjugation methods that have been applied to doxorubicin, as well as to SN-38, the active principle of irinotecan (CPT-11), a potent drug used in the treatment of metastatic colorectal cancer. Thus, we intend this to be the first in a series of clinical studies to evaluate the therapeutic opportunities for our antibody-drug conjugates."

Source : money.cnn.com


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AVEO's Tivozanib Demonstrates Anti-Tumor Activity in Engineered Lung Tumors Exhibiting Treatment Resistant Mutations

AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today announced data which demonstrates that tivozanib (AV-951) – the company's oral, triple VEGF receptor inhibitor – exhibits potent anti-angiogenic and anti-tumor activity in AVEO's proprietary in vivo lung cancer models.

Specifically, treatment with tivozanib resulted in complete tumor growth inhibition or tumor regression (shrinkage) in lung tumors driven by EGFR or KRAS mutations, which are especially difficult to treat. These data are being presented today at the 13th World Conference on Lung Cancer (WCLC) in San Francisco, abstract number PD10.1.5.

"Non-small cell lung cancer is a highly heterogeneous disease and one of the most difficult cancers to treat. Common genetic alterations responsible for the disease, such as those driven by KRAS or certain EGFR mutations, typically render anticancer treatments powerless,” stated Murray O. Robinson, Ph.D., senior vice president, oncology at AVEO. “Utilizing our proprietary cancer biology platform, we have created and treated genetically-engineered lung cancer mouse models driven by treatment resistant EGFR or KRAS, resulting in a much more realistic, human-like environment in which we can evaluate tivozanib efficacy. We are very pleased with and encouraged by the robust activity demonstrated by tivozanib in these difficult-to-treat tumor alleles."

Tivozanib is a novel, oral triple VEGF receptor inhibitor which recently completed a Phase 2 clinical study and is expected to enter a Phase 3 clinical trial later this year in patients with advanced kidney cancer. Tivozanib is being studied in several ongoing Phase 1b/2a clinical trials. Clinical results to date suggest tivozanib is a potent, well tolerated anticancer agent with broad potential as a treatment for solid tumors.

"Our innovative, proprietary cancer biology platform helps us create more relevant models of cancer in which we can evaluate the efficacy of our drug candidates preclinically, thereby increasing the probability of success in the clinic,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “The robust anti-angiogenic and anti-tumor activity of tivozanib in AVEO-engineered models of TKI-resistant lung tumors, paired with the early results observed with tivozanib in patients with lung cancer from the previously reported Phase 1 trial, highlights the potential role of tivozanib in the treatment of this difficult-to-treat cancer.”

In this study, AVEO developed genetically engineered lung adenocarcinoma models driven by either treatment resistant EGFRT790M or KRAS mutant proteins by creating chimeric mice incorporating genetically modified ES cells. Tumors driven by EGFR or KRAS were propagated in vivo, to examine tivozanib activity in both subcutaneous and orthotopic settings. Treatment of subcutaneous lung KRAS tumors with tivozanib 2mg/kg and 5mg/kg daily PO for two weeks resulted in complete tumor growth inhibition and 44 percent tumor regressions respectively. Lung EGFR tumors were tested in an orthotopic setting by intravenous seeding. Tivozanib treatment was initiated after tumor establishment was detected by in vivo imaging; 5 mg/kg daily dosing for more than 10 days resulted in prolonged survival. Histologic analysis showed the same dramatic anti-angiogenic changes as in the subcutaneous KRAS tumors, indicating that tivozanib is effective in killing orthotopic lung tumors that are resistant to EGFR targeted kinase inhibitors (TKIs).

In a previously reported Phase 1 dose-escalation study evaluating tivozanib in 41 patients with advanced solid tumors clinical benefit (i.e., partial response or stable disease lasting for three months or longer) was achieved across multiple tumor types, including in those patients with lung cancer. Overall, tumor shrinkage was observed in 33 percent of all patients during treatment with tivozanib. A Phase 1b/2a trial evaluating tivozanib as monotherapy in patients with non-small cell lung cancer was initiated in March 2009 and is ongoing.

In May 2009, researchers presented complete Phase 2 data evaluating tivozanib in metastatic renal cell carcinoma (mRCC) at the 45th Annual Meeting of the American Society for Clinical Oncology (ASCO), which demonstrated prolonged progression-free survival of 11.8 months and an excellent safety profile in patients treated with tivozanib. The company expects to initiate a Phase 3 trial of tivozanib in advanced kidney cancer later this year.

Source : www.drugs.com


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Scientists Test New Way to Get Drugs to Cancer Cells

Nanoparticles that can carry cancer-killing radioisotopes directly to tumors show promise, U.S. researchers report.

The nanoparticles are made with liposomes, small chemical spheres made of fatty molecules that can be designed to carry a number of drugs and chemicals, and can be manipulated to control how long they remain in the bloodstream.

Johns Hopkins University researchers attached cancer-specific antibodies to liposomes to create immunoliposomes that travel through the bloodstream and seek out tumors. When they come in contact with tumors, the immunoliposomes deliver their payload into cancer cells.

"It's a promising approach to solving the problem of how to deliver more of a therapeutic to cancer cells," research leader and radiology professor George Sgouros said in a news release from the American Association of Physicists in Medicine.

The research was to be presented July 28 at the association's annual meeting, in Anaheim, Calif.

In a study on mice, Sgouros and his colleagues loaded the immunoliposomes with alpha-particle emitters, which are powerful radioisotopes that can kill cancer cells without damaging nearby healthy cells. The treatment substantially extended the survival of mice that had aggressive metastatic breast cancer.

"This treatment is much less toxic than chemotherapy because it is targeted to tumor cells rather than to all rapidly dividing cells," Sgouros said. "Nanoparticles designed to deliver these powerful isotopes have a great potential in cancer therapy, particularly for metastatic disease."

Source : www.drugs.com




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