Leading expert in colorectal cancer precision medicine, Dr. David Kerr, MD, explains how tumor biomarkers like KRAS, NRAS, and microsatellite instability (MSI) are essential for selecting the best chemotherapy and avoiding unnecessary toxic treatments, thereby personalizing care and improving patient outcomes in both early and advanced-stage disease.
Colorectal Cancer Biomarkers: A Guide to Precision Treatment and Personalized Therapy
Jump To Section
- Precision Medicine Defined
- KRAS and NRAS Mutations
- Avoiding Unnecessary Treatment
- Microsatellite Instability (MSI)
- Integrating Biomarkers into Treatment
- The Role of Second Opinion
- Future of Colorectal Cancer Care
Precision Medicine Defined
Precision medicine in colorectal cancer treatment builds upon traditional personalization methods. Dr. David Kerr, MD, clarifies that oncologists have always personalized care using factors like a patient's age and overall fitness for therapy. The new element is the systematic adoption of molecular tumor markers that allow for precise patient segmentation. This approach ensures that specific therapies are matched to the patients most likely to benefit from them, moving beyond a one-size-fits-all strategy.
This evolution represents a significant shift towards data-driven oncology. Dr. Anton Titov, MD, notes that this method maximizes treatment efficacy while minimizing potential harm.
KRAS and NRAS Mutations
KRAS and NRAS mutations are critical predictive biomarkers in advanced colorectal cancer. Dr. David Kerr, MD, explains that tumors harboring mutations in these genes will not respond to EGFR (Epidermal Growth Factor Receptor) inhibitor therapies. Testing for these mutations is now a standard part of the diagnostic workup for metastatic disease.
This genetic testing prevents approximately 35% to 40% of patients from receiving a costly and potentially toxic treatment that offers them no benefit. By focusing EGFR-targeted chemotherapy only on patients with wild-type (non-mutated) KRAS and NRAS genes, oncologists can significantly improve response rates.
Avoiding Unnecessary Treatment
A primary goal of precision medicine is to help colorectal cancer patients avoid unnecessary and toxic chemotherapy. Dr. David Kerr, MD, emphasizes that biomarkers provide the evidence needed to confidently withhold treatment when it is unlikely to help. This directly spares patients from side effects like neuropathy, fatigue, and nausea without compromising their oncologic outcome.
Dr. Anton Titov, MD, highlights that this avoidance of futile therapy is a major victory for patient quality of life. It allows individuals to preserve their strength and well-being during a challenging time.
Microsatellite Instability (MSI)
Microsatellite instability (MSI) is a crucial prognostic and predictive biomarker, particularly in early-stage colorectal cancer. Dr. David Kerr, MD, describes how pathologists test resected tumors for DNA mismatch repair deficiency, which is the cause of MSI. Patients whose tumors display high levels of microsatellite instability (MSI-H) are known to have a naturally favorable prognosis.
For these patients, especially those with stage 2 colon cancer, the data shows that adjuvant chemotherapy provides little to no additional benefit. Therefore, a finding of MSI-H often leads to the decision to forgo chemotherapy after surgery, relying instead on the good prognosis associated with this biomarker.
Integrating Biomarkers into Treatment
Integrating multiple biomarkers creates a comprehensive genetic profile to guide colorectal cancer therapy selection. The combination of KRAS, NRAS, BRAF, and MSI status provides a powerful map for oncologists. This profile informs decisions across the treatment spectrum, from selecting the right first-line chemotherapy to determining the utility of surgery for metastatic lesions.
Dr. David Kerr, MD, confirms that this tumor genetic profile is absolutely necessary to guide modern treatment. This holistic approach ensures that every therapeutic decision is informed by the unique biology of the patient's cancer.
The Role of Second Opinion
Seeking a second opinion on advanced colorectal cancer is a critical step for confirming a diagnosis and treatment plan. Dr. Anton Titov, MD, explains that a second opinion provides confidence that the diagnosis is correct and complete, including all necessary biomarker testing. It also confirms that a curative approach is still possible, even with stage 4 metastatic disease to the liver or lungs.
This process helps patients choose the best precision medicine and targeted chemotherapy options available. Consulting with a major cancer center ensures access to the latest advancements and expertise in personalized treatment strategies.
Future of Colorectal Cancer Care
The future of colorectal cancer care is increasingly driven by the discovery and application of novel biomarkers. Dr. David Kerr, MD, points to the growing number of tumor markers that continue to refine precision medicine treatment. Research is ongoing to identify new targets and develop corresponding therapies, making the treatment landscape more complex and more effective.
Dr. Anton Titov, MD, concludes that this progress underscores the importance of care at specialized centers familiar with these advancements. The reliability and utility of tumor markers will only increase, further personalizing and improving outcomes for colorectal cancer patients.
Full Transcript
Dr. Anton Titov, MD: You are an international authority in precision medicine approach to colon cancer. You also specialize in rectal cancer diagnosis and treatment. How do predictive biomarkers help to select colorectal cancer patients? How do biomarkers help to match colorectal cancer patients with the correct targeted therapies?
Dr. David Kerr, MD: I find the terminology we use in modern cancer medicine to be interesting. We talk about personalized medicine. It is precision medicine. But, of course, all medical treatment for colorectal cancer is personalized. At the moment, we use conventional biochemical indices, patient's age, and performance status. We decide how fit the patient is for cancer therapy. We personalize colorectal cancer treatment. This is not something that's new.
What is new is the increasing adoption of molecular tumor markers. Precision medicine allows us to select and segment colorectal cancer patients who would benefit most from particular therapy of colon or rectal cancer. This is best seen with EGFR inhibitors, Epidermal Growth Factor Receptor pathway inhibitors. We look for mutated KRAS gene. Sometimes a patient has a mutant KRAS oncogene. This colon cancer patient will not respond to an EGFR inhibitor.
Therefore, testing for KRAS mutation prevents needlessly treating 35% to 40% of colorectal cancer patients whose tumors are mutant KRAS positive. We have to focus targeted colon cancer therapy on those patients who would benefit most from such treatment. All patients and the health economy would benefit from the use of molecular markers in precision medicine.
We use other conventional molecular markers in colorectal cancer diagnosis and treatment in Oxford. We use microsatellite instability (MSI).
Dr. Anton Titov, MD: Patients may have early-stage colorectal cancer. There is also stage 2 and stage 3 colon cancer after surgical operation. Pathologists give oncologists information about DNA mismatch repair deficiency in resected colorectal tumors.
Dr. David Kerr, MD: We know MSI proficiency (microsatellite instability, MSI). Colorectal cancer patients that have microsatellite instability in tumors have a really good prognosis. We tend not to give them adjuvant chemotherapy, especially in stage 2 colorectal cancer. This is an example of conventional predictive biomarkers used daily in the treatment of colorectal cancer.
Dr. Anton Titov, MD: Predictive biomarkers also help colorectal cancer patients to avoid unnecessary treatment. You just mentioned this about tumors with microsatellite instability. Avoiding unnecessary toxic chemotherapy is important. Chemotherapy has no proven benefit in certain colon cancer patients. Avoiding chemotherapy can increase the quality of life of patients.
Dr. David Kerr, MD: That is very important.