PROVIDENCE, R.I. [Brown University] — Interrupting one function of a protein that plays a key role in cell signaling could enable the development of new cancer treatments, according to a study led by Dr. Martin Taylor at the Warren Alpert Medical School of Brown University.

Cells communicate with each other and sense their environment using protein networks called signaling pathways, said Taylor, an assistant professor of pathology and laboratory medicine who is affiliated with Brown’s Center on the Biology of Aging and Legorreta Cancer Center. The more important a pathway is for cell survival, the more likely it is to be hijacked by cancer cells. The most commonly altered pathway in cancer is PI3K–mTOR–Akt, and the team’s discovery centers on mTOR, the protein at its center. 

What makes mTOR unusual is that it is the working engine of two different protein complexes, mTORC1 and mTORC2, and each does something different. Most cancer drugs targeted at mTOR affect both complexes — a challenge, Taylor said, because shutting down the mTORC1 complex has the unintended effect of making cancer cells more resistant to chemotherapy. 

In a study published in Science, Taylor and a team of scientists from across the nation showed how mTORC2 recognizes its targets, and how blocking only the mTORC2 complex, without touching mTORC1, could shut down growth signals to cancer cells. The findings suggest a path toward new cancer treatments — something the researchers are already working on.

“This helps point the way toward designing drugs that target the cancer-relevant side of the pathway without triggering survival pathways that protect the tumor,” said Taylor, first author of the study. “We are excited to share this story because we were able to answer a number of open questions that are important in basic biology and also have therapeutic implications.”

Taylor discussed the team’s findings and potential next steps in a Q&A with the Warren Alpert Medical School.