The discovery of a new type of cancer drug, a PI3K inhibitor, by scientists at The Institute of Cancer Research and collaborators is creating a stir in the cancer research community.
PI3K inhibitors target an enzyme known to be important for cancer growth and spread, and also for drug resistance. The drug works by blocking the PI3 kinase pathway, which is often hijacked in human cancers. It may have potential in a wide-range of human cancers, and scientists hope it will target cancer cells and spare healthy cells.
A number of PI3K inhibitors are being tested in patient trials around the world, including the drug called GDC-0941 that was discovered at the ICR in collaboration with biotech company Piramed and licensed to Genentech/Roche.
Now new figures reveal that a paper on the discovery and properties of the drug and its progress through the development pipeline was the most highly-cited review published in Cancer Research in 2010. Cancer Research is itself the most frequently cited cancer journal in the world. The article - written by Professor Paul Workman, Dr Florence Raynaud and colleagues in the ICR’s Cancer Research UK Cancer Therapeutics Unit - was also the journal’s third most referenced paper overall for that year, meaning that scientists around the world consider it to be the authoritative view on the topic.
The new recognition comes after an article by the same team describing the original discovery of early PI3K inhibitors was singled out by a leading cancer journal for the current and future impact it is having on patients. Last year, that paper was selected as one of 16 studies published in Molecular Cancer Therapeutics that have had the greatest “patient impact factor” - a lasting impact on research and patient care. The “outstanding” articles were selected from more than 9,500 the journal has reviewed and 3,700 it has published over the past decade.
“Before we started this research project, PI3 kinase-inhibitory drugs were unprecedented and the approach was generally viewed as high risk by the pharmaceutical industry,” Professor Workman says. “Our discovery and subsequent development of these inhibitors was critically important because a high proportion of cancers have abnormalities in the PI3 kinase pathway, and so these drugs have the potential to treat a wide range of human cancers as a form of personalised medicine.”
Studies led by the ICR have previously shown that the drug successfully inhibited the PI3 kinase pathway and blocked tumour growth. In mice, growth of glioblastoma - the most common form of brain tumour – was reduced by 98 per cent and growth of ovarian cancer decreased by 80 per cent.
A number of Phase I studies are underway testing GDC-0941 as a single treatment for solid tumours or non-Hodgkin's lymphoma. GDC-0941 is also being tested in combination with other targeted medicines for metastatic breast cancer and metastatic non-small cell lung cancer.
The PI3K articles:
Cancer Research: Drugging the PI3 Kinome: From Chemical Tools to Drugs in the Clinic. Workman, et al. Cancer Res March 15, 2010 70:2146-2157
Molecular Cancer Therapeutics: Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Workman, et al. Mol Cancer Ther. 2009 Jul;8(7):1725-38. Epub 2009 Jul 7