New Therapeutic Target for Cancer Identified

Attacking pseudoenzyme kinase suppressor of RAS (KSR) could be a potential therapeutic option for targeting Ras-dependent aggressive cancers, such as pancreatic cancer and lung cancer, according to a study published in Nature.

This pseudoenzyme plays a critical role in the transmission of signals inside the cell, which determines if the cells will grow, divide, or die off. Although prior studies have supported the potential for targeting oncogenic forms of Ras — the most frequently mutated cancer gene – through KSR, there have been no approaches reported until now.

“New drug targets for Ras-dependent cancers have long been sought,” said lead researcher Arvin Dar, PhD. “We used data on known genetic variants in KSR that suppress mutant Ras signaling to guide the development of novel compounds. In this way our study took a very different approach as we have used chemistry to mimic genetic mechanisms that are able to block the development of Ras-dependent cancers.”

The results of the study showed that the lead compound APS-2-79 can modulate Ras signaling, and increase the potency of several other cancer drugs within the RAS-mutant cell lines.

“KSR belongs to a large class of proteins that are not only implicated in the development of cancer, but also other diseases as well,” Dar said. “No one has really figured out how to exploit these important drug targets. Our study opens the possibility of modulating KSR as a new cancer therapy and also potentially an entirely new class of interventions.”