Mutations in a gene called KRAS are found in up to 25% of lung cancers, 45% of colon tumors and 90% of pancreatic cancers. Yet after three decades of research, no effective treatments targeting KRAS mutations have been developed. Germany’s Boehringer Ingelheim hopes to turn around that streak of bad luck via a partnership it has formed with Vanderbilt University.
BI is teaming up with scientists at Vanderbilt to pursue a novel target called SOS (Son Of Sevenless), which is a protein that activates the cancer-causing KRAS gene. The partnership builds upon a 2015 research pact the company formed with the university to develop KRAS-targeting treatments, according to a press release.
BI has been investigating many potential ways to inhibit KRAS, both directly and indirectly. The company intends to develop small molecules to inhibit SOS—in essence making an end run around mutated KRAS but shutting off a key switch that activates it. The work is based on discoveries made by Stephen Fesik, a cancer researcher at Vanderbilt, according to the release.
“With new technologies and the scientific discoveries made by Professor Fesik’s laboratory, we believe the time is now right to step up research efforts to develop novel cancer treatments that work by attacking KRAS and associated signaling pathways,” said Clive Wood, Ph.D., senior corporate vice president of discovery research at BI, in the release.
BI remains committed to conquering KRAS despite a history of setbacks suffered by other biopharma players. Last August, for example, AstraZeneca posted disappointing data from a phase 3 trial of selumetinib, a designed to treat KRAS-mutation-positive non-small cell lung cancer by inhibiting the protein MEK. The drug had previously failed a trial in uveal melanoma.
Bind Therapeutics slid into bankruptcy in 2016 after its drug targeting KRAS-mutation-positive lung cancer, BIND-014, charted disappointing results in lung cancer. Pfizer bought the company in a bankruptcy auction for $40 million.
BI has already chalked up some milestones in its collaboration with Fesik’s lab at Vanderbilt, which began in 2015. Since then, the partners have identified lead compounds that bind to KRAS “with high affinities,” BI says.