BRAF and KRAS Mutations Can Help Drive Treatment Decisions
- Colorectal cancer cases are increasing in younger adults. But at the same time, treatment is becoming more precise, more personalized, and more hopeful.
- Today, doctors are increasingly looking at the genetic makeup of each patient’s tumor to guide treatment decisions. These are called molecular or genomic markers and they’re transforming how colorectal cancer is treated. Some of the most important of these markers are BRAF and KRAS mutations.
- When doctors talk about BRAF and KRAS, they’re referring to genes inside cancer cells. These genes help control how cells grow and divide. When they’re mutated, they can act like a stuck accelerator, causing cancer to grow more aggressively.
- Patients with advanced colorectal cancer should have genetic testing to ensure they are receiving the most effective treatment possible.
“Instead of having a one-size-fits-all approach, we look at what’s driving the tumor in that individual patient and try to match the treatment to it,” Dr. Nicholas Hornstein, a gastrointestinal medical oncologist at Northwell’s Lenox Hill Hospital who specializes in colorectal cancer, tells SurvivorNet.
Read MoreWhat Are BRAF & KRAS Mutations?
When doctors talk about BRAF and KRAS, they’re referring to genes inside cancer cells. These genes help control how cells grow and divide. When they’re mutated, they can act like a stuck accelerator, causing cancer to grow more aggressively. Testing for these mutations is done through tumor genetic profiling, something that is becoming standard for many patients, especially when cancer has spread.KRAS: The Most Common Mutation
KRAS mutations are found in about 30-40% of colorectal cancers. For patients, this mutation is important because it can determine which treatments will not work.
For example, some commonly used targeted therapies (like those that inhibit the EGFR gene) are ineffective if KRAS is mutated.
National Comprehensive Cancer Network (NCCN) guidelines specify that patients with any known KRAS mutation should not be treated with anti-EGFR antibodies, unless given as part of a regimen targeting a KRAS G12C mutation. Identifying a KRAS mutation can help avoid unnecessary treatments and move patients quicker towards better options.
For KRAS-mutant metastatic colorectal cancer, the NCCN guidelines recommend chemotherapy-based regimens with bevacizumab (anti-VEGF therapy) rather than anti-EGFR therapy.
Dr. Horstein stresses that patients should talk to their doctors about whether genetic testing is needed.
“Ask your oncologist: has my tumor been genetically tested? If not, the next question is why,” he explains.
A major recent advance is the development of KRAS G12C-specific inhibitors (sotorasib and adagrasib), which can be used in combination with anti-EGFR antibodies for patients with KRAS G12C-mutated metastatic colorectal cancer after prior chemotherapy.
An important study, called the CodeBreaK 101 trial, demonstrated a 30% confirmed response rate with sotorasib plus panitumumab compared to 9.7% with sotorasib alone in chemorefractory KRAS G12C-mutant colorectal cancer. Both drugs are FDA-approved in combination with cetuximab or panitumumab for this specific type of cancer.
BRAF: More Aggressive, But Targetable
Like the KRAS mutation, BRAF gene mutation happens randomly and it’s not hereditary. BRAF mutations are less common (about 10% of cases) but carry significant weight.
BRAF mutations have historically been associated with more aggressive disease and worse outcomes. But now, targeted therapies are changing that reality.
All patients with metastatic colorectal cancer should have BRAF mutation testing as part of multigene panel testing at initial diagnosis.
“We’ve known for a long time that BRAF-mutated colorectal cancers are more dangerous. Now we have treatments that can more than double survival,” Dr. Hornstein explains.
The treatment landscape for BRAF V600E-mutant metastatic colorectal cancer has evolved dramatically. The NCCN guidelines now recommend encorafenib plus cetuximab (or panitumumab) combined with regular chemotherapy (FOLFIRI or FOLFOX) as preferred first-line therapy.
How is Genetic Testing Performed?
Genetic testing for mutations like BRAF and KRAS is usually done using a sample of the tumor itself.
In most cases, this means:
- Tissue from a biopsy or surgery is sent to a specialized lab
- The lab analyzes the tumor using advanced techniques (often called next-generation sequencing, or NGS) to look for specific mutations
If there isn’t enough tumor tissue available, or if doctors want more up-to-date information, they may also use a blood test, sometimes called a liquid biopsy, which looks for tiny fragments of tumor DNA circulating in your bloodstream.
You usually don’t need an additional invasive procedure as testing is often done using tissue that has already been collected.
A New Era Of Precision Medicine
As knowledge about colon cancer continues to evolve, it’s becoming increasingly clear that testing for mutations like BRAF and KRAS is a critical step in making sure patients receive the most effective treatment possible.
Today, the right way to treat cancer varies from patient to patient, and that shift from generalized care to precision medicine is already changing outcomes.
A cancer diagnosis is never easy, but advances like these should give patients hope.
Questions To Ask Your Doctor
- Has my tumor been tested for KRAS and BRAF mutations?
- How do these results affect my treatment options?
- Are there targeted therapies that might work for me?
- Should I consider additional genetic testing?
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