Pathway of dealiest cancers blocked by potential new drug

Scientists from Cancer Research Technology Ltd (CRT) presented new findings at the 2009 AACR Meeting, Denver, showing that a potent and selective inhibitor of protein kinase D called CRT0066101, inhibits the growth of pancreatic tumours.

The research - presented by CRT’s Dr Christopher Ireson - was a collaborative effort between scientists at CRT’s discovery laboratories and the University of Texas MD Anderson Cancer Center. These results show for the first time that an inhibitor of PKD can slow the growth of tumours in pancreatic cancer models. In addition, experiments carried out by CRT have shown that CRT0066101 is also effective at inhibiting the growth of tumours in a lung cancer model. The scientists believe that the drug has the potential to treat other cancers too.

PKD is a relatively newly identified family of serine/threonine kinases comprising PKD1, PKD2 and PKD3. The potential of PKD as a new drug target was discovered by Enrique Rozengurt, Doreen Cantrell and Peter Parker and funded by Cancer Research UK. Following this discovery, an intensive drug discovery effort led by CRT’s Head of Medicinal Chemistry, Dr Tony Raynham, cumulated in the identification of CRT0066101 as a lead candidate for pre-clinical studies. Since then, PKD has been identified as playing a central role in the development of a number of cancers. In addition to its role in the growth of tumour cells, PKD has also been shown to play a pivotal role in cell survival and angiogenesis - a process by which tumours form new blood vessels - which is central to tumour growth and spread.

CRT’s discovery laboratories director Dr Hamish Ryder said: “We focused on pancreatic and lung cancer tumours because they represent cancers with a significant unmet medical need. “The CRT model of combining promising basic science with the capability of the industrially-focus Discovery Laboratories gives us a unique opportunity to rapidly develop potential new molecules to novel targets, and through partnering with industry, explore the potential to see if one day it might help treat cancer patients in the future”.

Dr Sushovan Guha who leads the laboratory at MD Anderson Cancer Center, said: “We are very optimistic about CRT0066101’s pharmacological potential. We believe this is the first orally administered small-molecule inhibitor of PKD with significant biological efficacy in pre-clinical animal models of pancreatic cancer. My conviction is that we will show the drug can also prevent the proliferation of cancer cells by blocking their supply of blood - through neo-angiogenesis. This would mean it offers a double action treatment but this needs to be proved through further work.”

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