Leading expert in colorectal cancer immunotherapy, Dr. Heinz-Josef Lenz, MD, explains how molecular tumor marker testing is critical for treatment decisions. He details the concept of molecular escape, where colon cancer cells evolve to resist therapy, and highlights the role of liquid biopsy in real-time monitoring. Dr. Heinz-Josef Lenz, MD, emphasizes that BRAF, microsatellite instability (MSI), KRAS, and NRAS testing are essential for identifying patients who will benefit from immune checkpoint inhibitors and other targeted treatments.
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Understanding Molecular Escape and Immunotherapy in Colon Cancer
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- Molecular Testing for Immunotherapy
- Rare Mutations and Treatment Decisions
- The Concept of Molecular Escape
- Liquid Biopsy for Monitoring
- Immunotherapy and Patient Selection
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Molecular Testing for Immunotherapy Decisions
Dr. Heinz-Josef Lenz, MD, states that BRAF, microsatellite instability (MSI), KRAS, and NRAS molecular tumor marker testing are absolutely critical for immunotherapy treatment decisions in colon cancer today. These biomarkers are essential for selecting patients who are most likely to respond to immune checkpoint inhibitors. Dr. Heinz-Josef Lenz, MD, explains that patients whose tumors display microsatellite instability (MSI) are particularly sensitive to these immune modulator medications.
Rare Mutations and Treatment Decisions
Dr. Heinz-Josef Lenz, MD, discusses the importance of testing for rare mutations, even those found in only 1% or 2% of colon cancer patients. This comprehensive approach ensures oncologists are prepared for subsequent targeted or immunotherapy treatments as they become available. There is an ongoing discussion among doctors about the integration of this additional genetic testing into standard clinical practice to advance precision medicine.
The Concept of Molecular Escape
A key challenge in colon cancer treatment is a phenomenon known as "molecular escape." Dr. Heinz-Josef Lenz, MD, explains that the colon cancer cells that survive chemotherapy are not the same as the cells that died. These surviving cells develop mechanisms to fight off the treatment, leading to tumor evolution and potential resistance. This means the genetic profile of the cancer can change over time during therapy.
Liquid Biopsy for Real-Time Monitoring
To address molecular escape, Dr. Heinz-Josef Lenz, MD, highlights the role of liquid biopsy. This incredible new technology allows doctors to monitor the evolution of colon cancer tumor cells in real time without requiring repeated invasive tissue biopsies. Liquid biopsy analyzes circulating tumor DNA from a simple blood draw, providing a dynamic view of the tumor's genetic changes as treatment progresses.
Immunotherapy and Patient Selection
Dr. Lenz confirms that colon cancer immunotherapy is effective, but currently works in only about 5-10% of patients. This underscores the vital importance of proper patient selection through molecular profiling. Identifying biomarkers like BRAF mutations and MSI status is the best way to predict immunotherapy success and offer advanced stage 4 colon cancer patients a chance at a durable response or even a cure.
Full Transcript
Dr. Anton Titov, MD, interviews Dr. Heinz-Josef Lenz, MD, a leading colorectal cancer expert. The discussion focuses on the critical need for molecular testing of BRAF, MSI, KRAS, and NRAS to guide immunotherapy decisions. Dr. Lenz introduces the concept of molecular escape, where tumor cells evolve to resist treatment, and champions liquid biopsy as a tool for monitoring these changes in real time. The conversation emphasizes that precision medicine, based on repeated genetic profiling, is essential for matching advanced colon cancer patients with the most effective targeted and immunotherapy treatments.
Full Transcript
Dr. Heinz-Josef Lenz, MD: BRAF, microsatellite instability (MSI), KRAS and NRAS molecular tumor marker testing are critical today for immunotherapy treatment decisions in colon cancer. The colon cancer cells that survived chemotherapy may not be the same as the cells that died.
Liquid biopsy can monitor in real time the molecular escape of colorectal tumor.
We already talked about the new immunotherapies available to treat metastatic colon cancer. They target the immune system checkpoints in metastatic colon cancer tumors.
Immune modulators in metastatic colon cancer are not as effective as in melanoma and non-small cell lung cancer. But we need to select those metastatic colon cancer patients who are very sensitive to immune modulator medications.
This patient population is usually characterized by a status of microsatellite instability (MSI) of their colon cancer tumor.
BRAF, microsatellite instability (MSI), KRAS and NRAS molecular tumor marker testing are absolutely critical today for immunotherapy treatment decisions in colon cancer. These molecular markers are particularly important.
We should consider new colon cancer immunotherapy treatment regimens. They are usually not part of the standard treatment protocols that we offer to patients with colon cancer.
But we have to go beyond those decisions. There are very often mutations in cancer that are potentially treatable.
The question is, how often do we find mutations in patients with metastatic colon cancer? Some of these colon cancer tumor mutations may be found only in 1% or 2% of patients with colon cancer.
Should we test for these mutations in order to be ready for subsequent immunotherapy treatments? There is discussion among doctors about integration of the additional genetic testing in our clinical practice.
But there has been an incredible revolution of thinking about molecular testing in colon cancer. That is very important for everyone to know.
Because when we have a diagnosis of colon cancer, we do the molecular testing of colon cancer tumor. We find certain mutations, and then we treat the patient with colon cancer correctly.
Colon cancer tumor cells that survive are not the same cells that die. Over time, these colon cancer tumor cells that survive may not be the same.
They are not the same cells we tested as a majority of the cells at the time of diagnosis of colon cancer.
Dr. Anton Titov, MD: It's also an issue of temporal profiling of the colon cancer tumor in evolution. Cancer treatment is adjusted to the evolving colon cancer tumor or remaining tumor cells.
Dr. Heinz-Josef Lenz, MD: Yes, and people call that "molecular escape." The colon cancer cells that survived may now not be the same as the cells that died.
Colon cancer cells that survive have a mechanism to really fight off the treatment of colon cancer.
How do we monitor evolution of colon cancer tumor cells in time? How can we go back to the colon cancer tumor as the treatment progresses?
Do we need to biopsy the colon cancer tumor again? It could be an invasive procedure. It depends where the tumor is located.
There has been an incredible new technology. It is called liquid biopsy.
Colon cancer immunotherapy works in 5-10% of patients. BRAF and MSI mutations predict immunotherapy success in colon cancer. Molecular escape of tumor is important to consider.