Precision Medicine in Colorectal Cancer: Integrating Tumor and Patient Genetics

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• Essential Tumor Biomarkers
• Comprehensive Genetic Panels
• Monitoring Tumor Evolution
• Patient Genetic Predisposition
• Impact on Younger Patients
• Future of Precision Oncology
• Full Transcript

Essential Tumor Biomarkers for Treatment Selection

Dr. Heinz-Josef Lenz, MD, states that testing for specific genetic mutations is absolutely critical for every patient diagnosed with metastatic colon cancer. The minimum biomarkers to obtain are KRAS, NRAS, BRAF, and Microsatellite Instability (MSI) status. These genetic markers are essential for predicting which targeted therapies and immunotherapies will be effective. This molecular profiling forms the foundation of personalized medicine, moving beyond a one-size-fits-all approach to colon cancer treatment.

The Role of Comprehensive Genetic Panels

Beyond the core biomarkers, Dr. Heinz-Josef Lenz, MD, explains that most oncologists now use larger gene panels that assess between 40 to 400 genetic mutations in a tumor. These extensive panels cover many additional genetic alterations that can have predictive value for selecting the best chemotherapy or prognostic implications for understanding a patient's likely outcome. Dr. Heinz-Josef Lenz, MD, believes the future of oncology lies in using these large panels to gain a deeper, more comprehensive understanding of individual tumor behavior.

Monitoring Tumor Evolution and Treatment Resistance

A significant advancement in precision medicine is the ability to monitor how a colon cancer tumor's genetic profile changes during treatment. Dr. Lenz describes how tumors attempt to escape the effectiveness of chemotherapy, a process known as molecular escape. By continuously profiling the tumor, oncologists can identify these resistance mechanisms. This allows them to adapt the treatment strategy in real-time, choosing the next best therapeutic option from the many new medications available.

The Critical Importance of Patient Genetic Predisposition

While tumor genetics are vital, Dr. Heinz-Josef Lenz, MD, emphasizes that the molecular makeup of the patient is equally important. Identifying patients with a genetic predisposition to colon cancer is crucial for risk assessment. This is particularly true for younger patients or those with specific tumor features like right-sided location or mucinous histology. Genetic testing can reveal hereditary syndromes like Lynch syndrome, which has profound implications for the patient's family members.

Unique Impact on Younger Colorectal Cancer Patients

Dr. Heinz-Josef Lenz, MD, highlights that the metastatic spread of colon cancer in younger patients can be different and often more aggressive. For these patients, identifying a genetic predisposition is not just about family risk; it can directly influence their own treatment options. For example, some hereditary conditions make tumors more susceptible to certain immunotherapies. Early identification through genetic counseling and testing can therefore guide more effective, personalized treatment strategies from the outset.

The Future of Precision Oncology and Prevention

The future of colorectal cancer care, as outlined by Dr. Heinz-Josef Lenz, MD, involves a dual approach: comprehensive molecular profiling of the tumor and genetic profiling of the patient. This integrated strategy will optimize treatment selection for advanced disease and revolutionize prevention. By identifying at-risk individuals before cancer develops, we can direct them into intensive screening programs. As Dr. Heinz-Josef Lenz, MD, notes, when high-risk patients are involved in screening, the goal is that no one dies of colon cancer anymore, making prevention the ultimate form of precision treatment.

Full Transcript

Colon cancer tumor profile panels assess 40 to 400 genetic mutations in tumors: KRAS, NRAS, BRAF, and MSI markers. Genetic analysis helps to predict chemotherapy toxicity, gene profiling to select chemotherapy, and DNA analysis to find people at risk for colorectal cancers.

Colon cancer precision treatment is based on the genetic profile of the tumor and also includes the genetic profile of the patient. They interact in clinical colon cancer disease.

Dr. Anton Titov, MD: We already discussed colon cancer tumor biomarkers and personalized medicine for diagnostics and precision medicine for treatment of colon and rectal cancer patients. What are the most important genetic changes in the tumor in colon and rectal cancer? What genetic tumor changes might be the targets of future therapies for colon cancer?

Dr. Heinz-Josef Lenz, MD: I think it's very important. Absolutely critical molecular markers should be tested in each patient diagnosed with metastatic colon cancer: KRAS, NRAS, BRAF, and microsatellite instability. These colon cancer tumor markers are the minimum to obtain in every colon cancer patient.

Now, usually in the U.S., most of my colleagues use a panel of 40 to 400 genes for colon cancer molecular tumor profiling. These genes cover many additional genetic alterations in colon cancer tumors. Some mutations have potential for prediction of the best metastatic colon cancer treatment medication; some have prognostic implications for patients with colon cancer.

I think in the future we will all use a large colon cancer genetic mutation panel. It will help us better understand tumor behavior and prognosis for the colon cancer patient.

A lot has changed from a year or two ago. Previously we were able only to detect colon cancer tumor mutations at the time of diagnosis. Now we are able to monitor how the colon cancer tumor genetic profile changes during treatment. We can see how the colon cancer tumor tries to escape the effectiveness of chemotherapy. This helps to treat colorectal cancer better.

These mechanisms of tumor molecular escape may be critical to understanding cancer and determining the next best treatment option for the colon cancer patient. There are many different new medications available. We can choose the best colon cancer treatment based on continuous molecular profiling of the tumor. I think that is absolutely critical.

Now we talked a lot about the molecular makeup of the colon cancer tumor, but we have not talked about the molecular makeup of the colon cancer patient. We need to identify patients who may be at risk for certain cancers. Some patients have right-sided colon cancer before the age of 50. They have poorly differentiated carcinomas with mucinous features. These younger colon cancer patients are at higher risk to have a genetic predisposition for colon cancer.

This is important for identifying families at risk for colorectal cancer. We can direct them into genetic counseling and screening. Genetic testing of the patient at risk for colon cancer development is crucial. For patients who already have colon cancer, the diagnosis has predictive and prognostic implications for colon cancer development in the entire family.

The metastatic spread of colon cancer in younger patients is different. Access to potential immunotherapy for colon cancer is showing incredible promise. Identifying these patients with colon cancer early is important. It will have an impact on the individual patients and help predict cancer risk in their families.

We know that identifying patients with a genetic predisposition to colon cancer is very important. Cancer screening helps. Sometimes patients at risk of colon cancer are involved in screening; then no one dies of colon cancer anymore.

I think we will have in the future a molecular profiling of the colon cancer tumor and also a molecular profiling of the patient. This is particularly true for genetic predispositions to colon cancer.

Dr. Anton Titov, MD: This is very important to know, because prevention of colon cancer is the best treatment.

That's correct. Colon cancer precision treatment depends on both tumor and patient's genetic profile. Molecular profiling of the patient is important. Stage 4 colon cancer chemotherapy.