Targeting a genetic mutation that causes many cancers

A study at MD Anderson Cancer Center has shown promise for effective treatment of therapy-resistant cancers caused by a mutation of the RAS gene that is found in many cancers. The pre-clinical study combined therapies targeting the inhibitors polyADP ribose polymerase (PARP) and mitogen-activated protein kinase (MEK). The findings were published recently in Science Translational Medicine.

Mutations in the RAS gene account for more than 90% of pancreatic cancers, 50% of colorectal cancers, 30% of lung cancers, and a significant portion of many other types of tumors. Unfortunately, these cancers are usually resistant to traditional treatments, contributing to poor patient outcomes.

“Nowhere is the need for targeted therapies greater than for cancers driven by oncogenic RAS, which represents the most common type of potentially targetable mutation in cancer,” said Gordon Mills, M.D., Ph.D., chair of Systems Biology. “Our study demonstrated that the rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with RAS-mutant tumors where there are few effective therapeutic options.”

Mills’ team found that combinations of PARP and MEK inhibitors evoked “unexpected cytotoxic effects” in vitro and in vivo in multiple RAS-mutant tumor models across tumor lineages where RAS mutations are prevalent. The combination therapy worked independent of mutations in tumor suppressor genes, including BRCA1, BRCA2 and p53, suggesting the dual therapy’s potential as a treatment for multiple RAS-mutant cancers. It also was effective for tumors that had become resistant to PARP, as well as in cells that did not have aberrations in BRCA1 and BRCA2, suggesting the combination could expand to a wide spectrum of patients likely to benefit.

Read more about the findings in the MD Anderson Newsroom.