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KRAS, The Most Common Biomarker For Lung and Other Cancers: What To Know
When patients go to the doctor or hospital for cancer care, they often find information with various abbreviations and acronyms that are common in medical lingo but are a mystery to patients and their families. Upon diagnosis, it is very important to ask your doctor for biomarker testing to see what cancer mutations you have. This can be accomplished by a biopsy of your tumor as well as by a blood test, referred to as a liquid biopsy. KRAS is the most common biomarker of a gene that drives a particular cancer (oncogene). KRAS is the most common biomarker associated with lung (32%), colorectal (40%), pancreatic (85%) and some other cancers. The focus of this blog is on the KRAS biomarker, and we hope to answer some of the questions you might have.
What is KRAS?
Although KRAS is a gene, within the context of cancer it is also considered a biomarker, which is something that can be measured to help diagnose cancer, predict its course, and decide on treatments. Understanding more about a patient’s KRAS mutation can help doctors diagnose a patient’s disease and plan treatment by targeting the biomarker directly. KRAS was identified fifty years ago, and we now know there are different sub-types of KRAS that respond to treatments differently. This is why biomarker testing is so important. In addition, since cancers can also continue to mutate as they grow, which may introduce new biomarkers, it may be necessary to continue biomarker testing over the course of treatment to identify new targets.
KRAS stands for Kirsten rat sarcoma viral oncogene homolog. It is pronounced Kay-ras. To break down the acronym meaning slightly, an oncogene is a gene that can cause cancer, and when two genes have similar genetic information, they are homologues of each other.
What does a KRAS mutation do?
The KRAS gene produces a protein that provides important signals to cells related to how quickly they grow, mature and die. Mutated forms can allow cells to grow too much and develop into cancer. KRAS mutations can cause cancer in multiple parts of the body. KRAS mutations also not only cause tumors but also alter the microenvironment around the tumors that they cause, which inflames the area and suppresses the immune system cells that would normally respond to unusual growth in the body.
What are the different types of KRAS mutations?
There are a few different mutations that can affect the KRAS gene, and the proteins that it produces. The most common KRAS mutations are G12C, G12D, and G12R mutations. Proteins are made up of amino acids, and each of these mutations refer to where and how the amino acids are changed. Different KRAS mutations respond to treatment differently, so it is important for doctors and patients to determine which KRAS mutation the patient has.
How common is KRAS?
KRAS mutations are very common across multiple cancer types. Doctors and medical professionals see KRAS mutations in about 25% of all solid tumors in the body. About 50% of lung cancer cases with KRAS mutations have the G12C mutation, with the rest having other mutations. Although the incidence of KRAS mutations is somewhat higher in people who smoke, it is not found exclusively in smokers.
Why is KRAS hard to treat?
The first KRAS gene mutation was discovered in 1982, and for almost 40 years, scientists thought that the mutated protein was “undruggable,” because the surface of the protein lacked places for drugs to latch on to. As a result, scientists have had to explore other elements in the tumor microenvironment that KRAS produces as targets for drugs, but these approaches were often imprecise. Finally, researchers found an allosteric site on the mutated proteins that drugs can target. An allosteric site isn’t the active site, but another place where medications could alter the shape of the protein to affect the active site. This allowed them to develop lung cancer drugs that can affect the G12C mutation only.
How are KRAS cancers treated?
Current standard of care for patients with KRAS positive tumors include surgery, radiation, chemotherapy and immunotherapy, or a combination depending on the stage of their cancer. KRAS mutations have been difficult to treat because uncontrolled cell growth can enable tumors to evolve resistance to traditional chemotherapy treatments. There are currently two targeted therapies approved for G12C, with active new research in drug development. There are also clinical trials offering new therapeutics. It is important to make sure your doctor is up to date on new developments.
Be sure to listen to the Backstage @ Upstage podcast on ”Kicking Cancer” with our guest Terri Conneran, founder of KRAS Kickers.
Sources:
KRAS mutation: from undruggable to druggable in cancer | Nature
What’s new in KRAS mutation research? | MD Anderson Cancer Center
It’s KRAS Biomarker Lung Cancer. What Do I Do Now? | Lung Cancer Foundation of America
What is KRAS Cancer | KRAS Kickers
KRAS and Lung Cancer | American Lung Association
KRAS | Fight Colorectal Cancer