DPD Enzyme Biomarker Predicts Capecitabine Efficacy in Colon Cancer

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• DPD Enzyme as a Predictive Biomarker
• Stage 3 Colon Cancer Research Findings
• Precision Medicine in Treatment Selection
• Ongoing Clinical Trials and Validation
• Future Research Directions for DPD
• Full Transcript

DPD Enzyme as a Predictive Biomarker

DPD enzyme gene expression is a crucial predictive biomarker for colon cancer treatment. Dr. Hans-Joachim Schmoll, MD, discusses its role in precision medicine. The enzyme's activity inside cancer cells directly alters the metabolism of 5-fluorouracil-based chemotherapy. This discovery allows for more personalized and effective treatment strategies.

High DPD expression leads to faster metabolism and destruction of the chemotherapy drug capecitabine. This renders the treatment less effective for those patients. Identifying this biomarker before treatment begins is a significant advancement. It spares patients from ineffective therapy and its associated side effects.

Stage 3 Colon Cancer Research Findings

Research focused on patients with stage 3 colon cancer who experienced a relapse. Dr. Hans-Joachim Schmoll, MD, and his team published these important results. They found that patients with recurrent disease had the same chance of responding to oxaliplatin and 5-FU chemotherapy as before relapse. This finding was consistent and provided a foundation for further investigation.

The molecular makeup of relapsed tumors showed a specific characteristic. The expression of the DPD enzyme was a key differentiator. This altered metabolism was a critical factor in treatment failure for some patients. Dr. Anton Titov, MD, highlights the importance of this discovery in the interview.

Precision Medicine in Treatment Selection

Precision medicine uses biomarkers like DPD to select the most effective colon cancer treatment. For patients with low DPD expression, capecitabine combined with oxaliplatin is a highly effective regimen. This targeted approach maximizes the chemotherapy's efficacy and improves patient outcomes.

Conversely, patients with high DPD expression will not benefit from this combination. For these individuals, Dr. Hans-Joachim Schmoll, MD, recommends choosing an alternative chemotherapy regimen. A common alternative is the FOLFOX protocol. This strategy ensures every patient receives a therapy that has the highest probability of success.

Ongoing Clinical Trials and Validation

Large-scale clinical trials are currently validating the use of the DPD biomarker. Dr. Hans-Joachim Schmoll, MD, notes trials in Europe and the United States involving 12,000 patients. These trials often compare 3-month versus 6-month chemotherapy durations in stage 3 colon cancer.

A major advantage of these studies is the collection of tumor sample tissue. Researchers can analyze these samples for DPD enzyme gene expression. This allows for a direct comparison between the biomarker's presence and capecitabine therapy efficacy. The results will provide robust data to confirm the biomarker's predictive power.

Future Research Directions for DPD

The exact mechanism of the DPD gene in colon cancer tumors is not yet fully understood. Dr. Hans-Joachim Schmoll, MD, emphasizes the need for more clinical trials. Further research is essential to investigate this important enzyme's role completely. This will solidify its place in standard clinical practice.

Understanding DPD more deeply could lead to even more refined treatment algorithms. It may also open doors for developing new drugs that can overcome resistance mechanisms. The work of Dr. Schmoll and others is paving the way for a new era of personalized colon cancer care.

Full Transcript

DPD is an enzyme in colorectal cancer tumors that predicts response to Xeloda treatment. How do we use precision medicine in colorectal cancer treatment selection?

Dr. Hans-Joachim Schmoll, MD: Patients with recurrent colon cancer had the same chance to respond to oxaliplatin and 5-fluorouracil chemotherapy. Efficacy of capecitabine (Xeloda) in stage 3 colon cancer patients depends on DPD enzyme activity in the colorectal cancer tumor. Therefore, DPD enzyme is a biomarker for selection of patients for whom Xeloda plus oxaliplatin chemotherapy will work.

DPD enzyme predicts capecitabine colon cancer treatment efficacy. We showed important results that were published in a scientific article. We investigated patients with stage 3 colon cancer who had a relapse of cancer. We showed that patients with recurrent colon cancer had the same chance to respond to oxaliplatin and 5-fluorouracil chemotherapy as before the tumor relapse.

We also published that the molecular makeup of colon cancer tumors in patients who relapsed after treatment had a specific characteristic.

Dr. Anton Titov, MD: The expression of a particular enzyme inside cancer cells altered metabolism of 5-fluorouracil. Chemotherapy in such patients was metabolized and destroyed faster in tumors of patients with a mutation.

Dr. Hans-Joachim Schmoll, MD: We showed that efficacy of colon cancer treatment with capecitabine depended on expression of this enzyme. We still do not clearly know how the gene for this enzyme works in colon cancer tumors. We have to do more clinical trials in colon cancer patients to investigate this important enzyme.

The gene for this enzyme seems to be a strongly predictive biomarker for efficacy of capecitabine in stage 3 colon cancer patients. We now may have a good tumor biomarker. We can predict efficacy of chemotherapy with capecitabine and oxaliplatin in stage 3 colon cancer patients.

This biomarker can allow selection of patients for whom Xeloda plus oxaliplatin chemotherapy will work. For stage 3 colon cancer patients who will not benefit, we can choose another chemotherapy regimen, for example, FOLFOX.

There are clinical trials in Europe. There are also clinical trials in the United States. They compare duration of 3 months and 6 months of chemotherapy in stage 3 colon cancer. There are results available from these clinical trials. There are 12,000 patients in these clinical trials.

Many of such clinical trials for colon cancer patients collect tumor sample tissue. It can be analyzed. We should be able to test activity of this enzyme that predicts capecitabine efficacy. It is called DPD. We can test if DPD enzyme gene expression can predict efficacy of capecitabine in colon cancer patients.

You can go to the tumor samples that are collected from many patients. You can actually take a look at the enzyme. Then you can compare expression of DPD enzyme with efficacy of capecitabine therapy.

Dr. Anton Titov, MD: Correct. Thank you. DPD is a strongly predictive biomarker for efficacy of capecitabine (Xeloda) in stage 3 colon cancer patients. A leading colorectal cancer expert discusses selection of patients for capecitabine (Xeloda) combination therapy with oxaliplatin.