‘Undruggable’ Cancers Potentially Treatable By Targeting Growth Signals

"Undruggable" cancers related to a cell-signaling pathway have shown impressive resistance to therapy so far. Now, scientists may have found a new compound that works.

Growth-Related Defect In RAS/MAPK

Half of all cancer cases in humans involve defects in a cell-signaling pathway called RAS/MAPK.

This specific pathway plays a significant role in affecting cell functions such as growth, division, and death, according to Medical News Today.

Due to its association with cancer, scientists have been trying to target the RAS/MAPK for treatments. So far, there have been a lot of fruitless attempts, which led to researchers dubbing it as "undruggable."

Now, researchers from the Revolution Medicines may have found a compound that's capable of interfering with the pathway's functions, University of California San Francisco reports.

Scientists used to believe that defects in the RAS/MAPK pathway involve proteins getting stuck in its pro-growth mode, so that it is constantly growing and more prone to tumors.

However, more recent research reveals that cancer-linked mutations simply make the proteins hypersensitive to normal growth signals, so the volume of the entire RAS/MAPK pathway increases. In the case of this updated information, the study researchers theorized that blocking normal growth signaling could work in stopping the growth of the cancer.

A Compound For Slowing Down Growth

The new study, published in the journal Nature Cell Biology, shows that cancer growth can be slowed by suppressing the RAS/MAPK signaling with an experimental compound. It specifically inhibits SHP2 signaling, which is key in letting receptor proteins activate RAS.

This molecule, called RMC-4550, was found capable of significantly slowing down cancer growth in lung, skin, colon, and pancreatic cancer cell lines.

It was also successful on human lung cancers grown in animal models, as the compound blocked tumor growth or caused them to shrink. Minimal side effects were also recorded in mice.

"This was very exciting to me because it meant that the compound was not just arresting cell growth but actually killing cancer cells," senior author Trever Bivona, MD, PhD, a UCSF Health clinical oncologist, explains about the effects of RMC-4550 on the tumor.

The team is optimistic that the compound could also work on other cancers beyond the study's scope.

"Almost every major oncogene I can think of coopts this pathway in one way or another, and many of these cancers currently have no effective targeted therapies or eventually develop resistance to available targeted therapies," Bivona added.

Human safety and efficacy trials are planned for the latter half of 2018. For these trials, Revolution Medicines will be using a proprietary drug candidate called RMC-4630.