Philip A. Philip, MD, PhD
Nearly 35 years after its discovery as the first human oncogene, RAS
remains a frustrating target in anticancer therapy even as knowledge about the molecular drivers of malignancies continues to expand at a rapid pace. Thus far, no therapies aimed directly at RAS
mutations have been developed.
From Rats to Humans
The observation that RAS
genes could cause cancer was initially discovered in rat sarcomas; hence the name, RA for rat and S for sarcoma. These genes were later identified in humans in 1982. RAS
is a family of oncogenes that are present in all cells in the body and were the first oncogenes identified in human cancer cells.1
Oncogenes work as an on/off switch for cell division, and RAS
mutations affect this switch, not allowing the cells to switch off and causing them to grow uncontrollably, leading to the development of cancer.
Initiative, has said. McCormick is a professor emeritus at UCSF Hellen Diller Family Comprehensive Cancer Center in San Francisco.
The Research Bandwagon
mutations were initially discovered, there was a flurry of research into new drug possibilities, but these did not lead to effective treatments. Initially, there was hope that farnesyltrans- ferase inhibitors (FTIs) were the answer. However, testing found that, although FTIs did block HRAS
, the strategy did not prove effective in phase II trials for lung and pancreatic cancers, or in phase III trials for colorectal and pancreatic cancers.2
... to read the full story