RAS is classified as an oncogene, a type of gene which, when mutated, can directly contribute to the development of cancer. An abbreviation for rat sarcoma, RAS is the most frequently mutated oncogene identified across all human cancers. It is estimated that RAS mutations are found in approximately 20% of all cancer cases, accounting for a significant number of diagnoses annually worldwide.
SSCHRC for RAS Therapeutics is dedicated to advancing the discovery of new and effective treatments for cancers driven by the RAS mutation. Our investigators have considerable experience in studying RAS and its influence on cancer in laboratory settings and have been instrumental in developing and investigating RAS inhibitors in clinical trials. They are committed to advancing RAS-targeted therapies for the benefit of cancer patients.
RAS mutations essentially cause the RAS protein—which acts like a cellular 'traffic light' controlling growth—to be permanently switched to 'green'. This results in an uncontrolled, never-ending flow of growth signals within the cell. These continuous signals lead to the unchecked growth of the cell, ultimately resulting in a cancerous state.
While many possible alterations can change the protein's behaviour, most of these transform RAS into a constant growth stimulus. Furthermore, RAS mutations may also enable cancer cells to evade detection by the body's immune system. These seemingly simple mutations can lead to exceptionally complex cancers because RAS is part of an intricate network of cellular signalling interchanges. When this network is mutated, the perpetual flow of signals can make RAS-mutated cancers more challenging to treat than those without the mutation. Developing effective and durable ways to block RAS has been a long-standing, critical objective in RAS-driven cancer research.
RAS mutations are found in approximately one in four lung cancer cases.
RAS mutations are found in over half of colorectal cancer cases.
RAS mutations are found in up to nine out of ten pancreatic cancer cases.
RAS mutations are typically identified through next-generation sequencing carried out on a biopsy of the cancerous tissue. Increasingly, liquid biopsies, which involve the analysis of a blood sample, are also being utilised to detect these mutations. The mutations may be detected in one of several proteins belonging to the RAS family, including KRAS, HRAS, and NRAS.
For many years, RAS was widely considered an 'undruggable' target, meaning a simple way to switch off the protein and block its effects on cells was not available. However, a recent revolution in drug discovery has led to the development of numerous therapeutic approaches aimed at inhibiting the function of the RAS protein.
Researchers at SSCHRC have been investigating RAS mutations in the laboratory and working to develop targeted treatments for decades. They are uniquely positioned to rapidly advance the understanding of RAS-driven cancers and accelerate the development of new treatment options.
"This is an incredibly exciting period, as we now have many different types of drugs that can block RAS," states one of the Co-Directors of the RAS Therapeutics at SSCHRC. "These include small molecules that can block all forms of RAS or those specifically designed for certain RAS mutations, as well as cellular therapies and vaccines that target RAS. SSCHRC will be leading numerous clinical trials to explore how these emerging therapies can benefit patients."
Determining the most appropriate drug or drug combination for each patient requires centralised, expert knowledge. At SSCHRC, the RAS Therapeutics provides clinical trials of RAS therapeutics and works collaboratively to match patients with the most suitable clinical trials.
"RAS mutant tumours are highly complex and can often outsmart the drugs currently available," says the Chief of Strategic Partnerships and a Co-Director of the RAS Therapeutics at SSCHRC. "We anticipate that the best treatment strategies will ultimately involve combinations of therapies, customised for each individual patient's cancer. Our central goal is to integrate all our expertise to discover the optimal treatments for our patients."