Liquid Biopsy for Colon Cancer: Real-Time Monitoring and Precision Treatment

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• What is Liquid Biopsy?
• Circulating Tumor DNA vs. Circulating Tumor Cells
• Non-Invasive Monitoring Advantages
• Circulating RNA: A New Breakthrough
• Real-Time Treatment Tracking
• Future of Precision Oncology
• Full Transcript

What is Liquid Biopsy?

Liquid biopsy is a revolutionary diagnostic method for metastatic colon cancer. Dr. Heinz-Josef Lenz, MD, describes it as a technique that utilizes a simple blood sample from a patient. This blood is then analyzed to isolate circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) that have been shed from the tumor into the bloodstream. This process provides a molecular snapshot of the cancer without requiring an invasive tissue biopsy.

The core promise of liquid biopsy lies in its ability to perform comprehensive DNA profiling of the surviving cancer cells. As Dr. Heinz-Josef Lenz, MD, explains, this allows oncologists to observe genetic changes in the tumor as it evolves under the pressure of chemotherapy or targeted therapy. This real-time genetic analysis is a cornerstone of modern precision medicine for colorectal cancer.

Circulating Tumor DNA vs. Circulating Tumor Cells

A critical distinction in liquid biopsy is between circulating tumor DNA and circulating tumor cells. Circulating tumor DNA consists of genetic fragments released by dying cancer cells. Analyzing ctDNA reveals specific DNA mutations present in the tumor mass.

In contrast, circulating tumor cells are intact, living cancer cells found in the blood. Dr. Heinz-Josef Lenz, MD, emphasizes that because these cells are alive, clinicians can test both their DNA and their RNA. RNA analysis provides insight into gene expression, which is a more dynamic and immediate reflection of how the tumor is responding to treatment. Combining data from both ctDNA and CTCs offers a powerful, multi-faceted view of the cancer's biology.

Non-Invasive Monitoring Advantages

The primary advantage of liquid biopsy is its non-invasive nature. Unlike a traditional tumor biopsy, which is a surgical procedure with inherent risks like bleeding and infection, a liquid biopsy requires only a blood draw. This makes it a safer and far more tolerable option for patients, especially those who need repeated monitoring throughout their treatment journey.

Dr. Anton Titov, MD, confirms this key benefit with Dr. Lenz, who agrees that avoiding invasive procedures is a major step forward. The ability to frequently sample blood allows for continuous assessment of treatment efficacy and tumor evolution, enabling oncologists to make timely adjustments to therapy plans without subjecting the patient to repeated surgeries.

Circulating RNA: A New Breakthrough

A groundbreaking advancement in the field is the detection of circulating tumor RNA. Many researchers previously believed this was impossible because RNA degrades quickly outside of cells. However, Dr. Heinz-Josef Lenz, MD, and his team at USC, in collaboration with Liquid Genomics, have successfully developed technology to identify these RNA molecules in a patient's peripheral blood.

This discovery is particularly significant for drug development. While DNA mutations change slowly, medication-induced effects on RNA levels can be observed almost immediately. This allows researchers to confirm in real-time whether a new drug is effectively hitting its intended target within the tumor cells, dramatically accelerating the development of novel therapies.

Real-Time Treatment Tracking

Liquid biopsy enables real-time, molecular-level tracking of colon cancer treatment. By regularly analyzing blood samples, doctors can monitor how the genetic landscape of a tumor changes during therapy. This is crucial for identifying the emergence of resistance mechanisms—the ways a cancer "escapes" the effects of a drug.

Dr. Heinz-Josef Lenz, MD, explains that understanding these escape mechanisms directly informs the choice of subsequent therapy. When a treatment stops working, liquid biopsy can reveal why and help oncologists select the next most effective targeted treatment, creating a truly dynamic and personalized treatment strategy for stage 4 colorectal cancer.

Future of Precision Oncology

The future of precision oncology is deeply intertwined with the advancement of liquid biopsy technology. Dr. Heinz-Josef Lenz, MD, expresses great confidence that this tool will become a standard of care worldwide. It provides a unique opportunity to manage cancer as a dynamic disease, adapting treatment strategies as the tumor evolves.

The combination of DNA mutation analysis and RNA expression profiling from a simple blood test represents a paradigm shift. It moves cancer care from periodic, invasive assessments to continuous, non-invasive molecular monitoring. This approach promises to improve outcomes for patients with metastatic colon cancer by ensuring they are always on the most effective, personalized treatment possible.

Full Transcript

The full transcript of the discussion between Dr. Anton Titov, MD, and Dr. Heinz-Josef Lenz, MD, on liquid biopsy in colon cancer is available above. It provides a detailed exploration of circulating tumor cells, cell-free DNA, and the emerging role of RNA analysis in monitoring treatment progress and guiding precision medicine for advanced colorectal cancer patients.

Full Transcript

Dr. Anton Titov, MD: What is liquid biopsy? Why do circulating tumor cells hold so much promise in the treatment of stage 4 colorectal cancer? What about circulating cell-free tumor DNA and RNA in monitoring the progress of colon cancer treatment?

Liquid biopsy of colon cancer guides cancer treatment in real time. Liquid biopsy tests a patient's peripheral blood for circulating tumor cells and circulating cancer DNA and RNA.

Dr. Heinz-Josef Lenz, MD: I think liquid biopsy gives us the opportunity to utilize a normal blood sample. Blood can be drawn from the colon cancer patient. We can isolate circulating DNA from the colon cancer tumor from this blood sample. We can also isolate circulating colon cancer tumor cells.

It is very important to distinguish between circulating tumor cells and circulating tumor DNA. We can do all the DNA profiling of tumor cells that survived. We can use the circulating cell-free DNA.

Colon cancer tumor cells that survive the treatment release their DNA into the blood. We can see what has changed over time in the colon cancer tumor under evolutionary pressure from cancer treatment. It is a great new tool for precision medicine colon cancer treatment.

Recent trials have confirmed that we can detect the genetic tumor changes in the blood sample. They are the same changes that we would detect if we biopsied the tumor. This is liquid biopsy in a colon cancer patient.

I think liquid biopsy is a really reliable new technology. Liquid tumor biopsy will be utilized in the future around the world. I have no doubt.

What is the difference between circulating DNA and the circulating colon cancer tumor cells? The circulating colon cancer tumor cells are alive. On alive cells, you can test DNA and you can test RNA of the colon cancer tumor.

Gene expressions in colon cancer tumor cells is potentially more dynamic. Gene expression in tumor cells reflects changes during the treatment of the colon cancer patient. We can combine two cancer genetic information sources in liquid biopsy.

We can do tumor DNA mutation analysis on circulating colon cancer tumor DNA. We can do this while the patient is being treated. We can also study gene expression and RNA levels on circulating alive tumor cells.

This information from colon cancer liquid biopsy will be extremely helpful in the future. It will help us to understand how colon cancer tumor escapes treatment. These tumor treatment escape mechanisms may dictate the subsequent choice of therapy. It will be the most effective next treatment of colon cancer.

Dr. Anton Titov, MD: Liquid biopsy is a testing of the peripheral blood of patients. It does not require an invasive biopsy of a metastatic tumor?

Dr. Heinz-Josef Lenz, MD: That's correct. We have developed new tumor liquid biopsy technology here at USC. We did it together with a company called Liquid Genomics. For the first time, we can identify circulating RNAs in a colon cancer patient's peripheral blood.

This is an unbelievable achievement. It is very important for new medication development. Because a DNA genetic mutation doesn't happen very quickly overnight. DNA mutations in tumors happen over time.

But the effect of a new medication on RNA levels is immediate. You can see if your tumor medication works. You can see if the medication's target in the tumor is really hit. RNA liquid biopsy method will be very critical for new medication development in colon cancer.

Dr. Anton Titov, MD: The circulating RNA of the tumor gives a very important temporal profile of the tumor. Is it possible to detect circulating tumor RNA in the peripheral blood of cancer patients?

Dr. Heinz-Josef Lenz, MD: That's correct. It is possible to detect circulating tumor RNA in the peripheral blood of cancer patients. Many people thought it was not possible because RNA should be degraded outside the cells.

But we have now shown it is possible to detect circulating tumor RNA in peripheral blood. We will present our data in Vienna at the ESMO meeting. I think liquid biopsy of tumor is a very unique tool.

We will have very unique opportunities to monitor the treatment of a colon cancer patient in real time on a molecular level. We will detect DNA and RNA of cancer cells in the peripheral blood of the patient.

Liquid biopsy of colon cancer is sampling of tumor cells. Cancer DNA and RNA exists in peripheral blood. Liquid biopsy is a painless and increasingly effective tool to monitor cancer treatment.