RAS is an oncogene, which is a gene that when mutated causes cancer. RAS — an abbreviation for rat sarcoma — is the most commonly mutated oncogene in human cancer. RAS mutations are found in 20% of all cancers and account for an estimated 260,000 cases per year in the U.S. and 3.4 million cases per year globally.
Dana-Farber’s Center for RAS Therapeutics is dedicated to discovering new and effective treatments for RAS-driven cancers. Our investigators have years of experience studying RAS and its influence on cancer in the lab and developing and investigating RAS inhibitors in the clinic. They are committed to advancing RAS therapeutics to benefit patients with cancer.
What does a RAS mutation do?
RAS mutations cause the RAS protein, which acts a bit like a traffic light, to be permanently stuck on green. The result is a never-ending flow of growth signals into the cell. Those signals cause the cell to grow unchecked and become cancerous.
There are many possible mutations that can alter the behavior of this protein. Most of these alterations turn RAS into an always-on growth stimulator, but RAS mutations may also help cancer cells evade detection from the immune system.
RAS mutations may sound relatively simple, but they can result in extremely complicated cancers. Imagine, for instance, that always-on green light is an actual traffic light embedded in an interchange of multiple freeways, each with twisting clover leaves of entering and exiting traffic. That green light can cause chaos.
In a cell, rather than being part of a network of traffic interchanges, RAS is part of a network of cellular signal interchanges. Each interchange can also be mutated in ways that keep the signals flowing. As a result, cancers with RAS mutations can be harder to treat than those without RAS mutations. Finding ways to block RAS effectively and durably has been a long-sought goal in RAS-driven cancer research.
How will I know if I have a RAS mutation?
RAS mutations are typically detected via next-generation sequencing of a biopsy of cancer tissue. Liquid biopsies (analysis of a blood sample) are also being used to detect RAS mutations. The mutations might be detected in one of several different RAS family proteins including KRAS, HRAS, and NRAS.
RAS mutations are most commonly found in lung, pancreatic, and colorectal cancer. They are present in about one in four lung cancer cases, more than half of colorectal cancer cases, and nine out of ten pancreatic cancer cases.
Are there approved treatments for RAS mutations?
For a long time, RAS was thought to be “undruggable,” meaning there wasn’t an easy way to turn off RAS and block its effects on cells. But recently, a revolution in drug discovery has led to the development of numerous therapeutic approaches to inhibiting RAS protein function. Currently two are approved by the U.S. Food and Drug Administration and dozens of novel agents are moving into clinical testing.
Dana-Farber researchers have been investigating RAS mutations in the laboratory and working to develop treatments that target RAS for decades. They are uniquely positioned to rapidly advance knowledge about RAS-driven cancers and speed the development of new treatment options.
“This is an incredibly exciting time as there are many different types of drugs that block RAS, including small molecules that block all forms of RAS or those that block only specific types of RAS mutations, as well as cellular therapies and vaccines that target RAS,” says Andrew Aguirre, MD, PhD, a Dana-Farber medical oncologist who is co-director of the Center for RAS Therapeutics at Dana-Farber and associate director of the Hale Family Center for Pancreatic Cancer Research. “Dana-Farber will be leading many clinical trials to learn how these emerging therapies can help patients.”
How can I get RAS-targeted treatment for a RAS-mutated cancer?
Centralized expertise is required to determine the right drug or combination of drugs for each patient. At Dana-Farber, the Center for RAS Therapeutics will offer clinical trials of RAS therapeutics and will work collaboratively to match patients to appropriate clinical trials.
“RAS mutant tumors are very complicated cancers. They can very easily outsmart the drugs we have,” says Alice Shaw, MD, PhD, chief of Strategic Partnerships and a co-director of the Center for RAS Therapeutics at Dana-Farber. “We expect the best strategies will ultimately be combinations of therapies, tailored to each individual patient’s cancer. Our goal is to bring all our expertise together to find the best treatments for our patients.”
Learn more about clinical trials offered through the Center for RAS Therapeutics.