Newly discovered cancer mutations could boost drug discovery

A new ways of analyzing cancer mutations could boost drug development, say University of Maryland researchers.

Scientists at the University of Maryland, employing a statistical-analysis method they developed, have identified thousands of genetic mutations that they believe contribute to cancer growth. The fresh insight into these previously ignored mutations could pave the way to new targeted treatments.

The discovery, reported in the journal PLOS Computational Biology, arose from a new approach the Maryland team took to scrutinizing data from cancer patients. Rather than focusing on mutations in single genes from individual patients—a common method used in oncology research—they searched for genetic abnormalities shared within families of related proteins, according to a press release.

The University of Maryland researchers focused on mutations in specific subsets of proteins called protein domains. There are precise locations in protein domains where tumor-related mutations are likely to be found, and different proteins can share those domains even if they’re encoded by different genes.

"Maybe only two patients have a mutation in a particular protein, but when you realize it is in exactly the same position within the domain as mutations in other proteins in cancer patients, you realize it's important to investigate those two mutations," said senior author Maricel Kann in the release. The research team refers to those mutation clusters as “oncodomain hotspots.”

The scientists looked for those hotspots across 20 cancer types, including glioblastoma, breast cancer, melanoma and stomach cancer. Using their method, they identified 3,041 novel genetic abnormalities related to cancer, they reported.

The University of Maryland discovery builds on a growing trove of research tying newly discovered mutations to cancer risk, potential treatments and outcomes. Earlier this year, for example, scientists at the University of Toronto published their discovery of a set of genetic mutations they believe can be used to predict which prostate tumors are most likely to metastasize after treatment. And the National Institutes of Health announced they have tied eight subsets of cervical cancers to genetic abnormalities, some of which are already targetable with FDA-approved drugs.

What’s different about the University of Maryland research is that it proposes searching for cancer-causing mutations in an entirely new way. Studying oncodomains, the scientists say, could in turn point to new oncology drug targets. "Because the domains are the same across so many proteins," Kann said in the release, "it is possible that a single treatment could tackle cancers caused by a broad spectrum of mutated proteins."