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Gene expression profiling may help guide pancreatic cancer treatment

Pharmacogenomic profiling of circulating tumor cells in the bloodstream may help personalize the choice of chemotherapy for patients with pancreatic cancer, according to preliminary results from an ongoing prospective study presented at the Gastrointestinal Cancers Symposium.

Profiling circulating tumor cells through a simple blood draw offers a less invasive way to analyze the molecular makeup of tumor cells compared with biopsy tissue analysis.

This novel analysis, called pharmacogenomic profiling, is repeatable throughout treatment to monitor a patient’s response to therapy.

The strategy can be beneficial in pancreatic cancer care because tumor biopsy samples often are unattainable, according to background information provided by researchers.

“The purpose of this study was to investigate whether a pharmacogenomic analysis of circulating tumor and invasive cells could be used as a strategy towards this goal of personalized medicine,”Kenneth H. Yu, MD, assistant attending physician at Memorial Sloan-Kettering Cancer Center, said during a press conference held prior to the symposium.

The study included 50 patients with stage II-IV pancreatic adenocarcinoma who received one of 12 different drug combinations as recommended by their physicians.

Researchers obtained chemotherapy sensitivity and gene expression patterns from all 50 patients prior to starting chemotherapy, as well as the time when patients’ tumors progressed while on treatment.

At the time of analysis, 20 patients experienced had tumor progression on first-line chemotherapy treatment. Researchers analyzed circulating tumor cells among the 20 patients with disease progression.

Pharmacogenomic profiling predicted tumors would be sensitive to treatment in six patients, and it predicted intermediate effectiveness of treatment in another six patients. The model, developed by CellPath Therapeutics, predicted tumors would be resistant to treatment in the other eight patients.

“We found that treatment was significantly more effective in the sensitive group when compared with the resistance group,” Yu said.

Tumors in the sensitive group remained under control for a median of 7.3 months, compared with 3.7 months for tumors in the resistant group, study results showed.

“The bottom line is that patients receiving treatment predicted by our model to be more effective did better,” Yu said.

Researchers also performed exploratory analysis examining gene pathways.

They observed major differences in the E2F1 and NFκB pathways among patients with advanced pancreatic cancer who experienced disease progression.

“Pharmacogenomic profiling is a promising and exploratory tool for predicting treatment responses in pancreas cancer,” Yu said. “By profiling circulating and invasive cells from a simple tube of blood, this approach can be done repeatedly in the patients we are treating. Finally, exploratory gene pathway analysis may provide some insight into mechanisms that are important for cancer prognosis and treatment resistance.”

The researchers will continue to analyze data from the ongoing study, and conduct additional studies to validate the approach, Yu said.

For more information:

Yu KH. Abstract #142. Presented at: Gastrointestinal Cancers Symposium; Jan. 24-26, 2013; San Francisco.

Disclosure: The researchers report consulting roles with, stock ownership in and employment relationships with CellPath Therapeutics.

Pharmacogenomic profiling of circulating tumor cells in the bloodstream may help personalize the choice of chemotherapy for patients with pancreatic cancer, according to preliminary results from an ongoing prospective study presented at the Gastrointestinal Cancers Symposium.

Profiling circulating tumor cells through a simple blood draw offers a less invasive way to analyze the molecular makeup of tumor cells compared with biopsy tissue analysis.

This novel analysis, called pharmacogenomic profiling, is repeatable throughout treatment to monitor a patient’s response to therapy.

The strategy can be beneficial in pancreatic cancer care because tumor biopsy samples often are unattainable, according to background information provided by researchers.

“The purpose of this study was to investigate whether a pharmacogenomic analysis of circulating tumor and invasive cells could be used as a strategy towards this goal of personalized medicine,”Kenneth H. Yu, MD, assistant attending physician at Memorial Sloan-Kettering Cancer Center, said during a press conference held prior to the symposium.

The study included 50 patients with stage II-IV pancreatic adenocarcinoma who received one of 12 different drug combinations as recommended by their physicians.

Researchers obtained chemotherapy sensitivity and gene expression patterns from all 50 patients prior to starting chemotherapy, as well as the time when patients’ tumors progressed while on treatment.

At the time of analysis, 20 patients experienced had tumor progression on first-line chemotherapy treatment. Researchers analyzed circulating tumor cells among the 20 patients with disease progression.

Pharmacogenomic profiling predicted tumors would be sensitive to treatment in six patients, and it predicted intermediate effectiveness of treatment in another six patients. The model, developed by CellPath Therapeutics, predicted tumors would be resistant to treatment in the other eight patients.

“We found that treatment was significantly more effective in the sensitive group when compared with the resistance group,” Yu said.

Tumors in the sensitive group remained under control for a median of 7.3 months, compared with 3.7 months for tumors in the resistant group, study results showed.

“The bottom line is that patients receiving treatment predicted by our model to be more effective did better,” Yu said.

Researchers also performed exploratory analysis examining gene pathways.

They observed major differences in the E2F1 and NFκB pathways among patients with advanced pancreatic cancer who experienced disease progression.

“Pharmacogenomic profiling is a promising and exploratory tool for predicting treatment responses in pancreas cancer,” Yu said. “By profiling circulating and invasive cells from a simple tube of blood, this approach can be done repeatedly in the patients we are treating. Finally, exploratory gene pathway analysis may provide some insight into mechanisms that are important for cancer prognosis and treatment resistance.”

The researchers will continue to analyze data from the ongoing study, and conduct additional studies to validate the approach, Yu said.

For more information:

Yu KH. Abstract #142. Presented at: Gastrointestinal Cancers Symposium; Jan. 24-26, 2013; San Francisco.

Disclosure: The researchers report consulting roles with, stock ownership in and employment relationships with CellPath Therapeutics.

    Perspective

    This study shows that it is possible using a noninvasive methodology to identify tumor cells and characterize them at the molecular level. This is important because it does not require another biopsy of a patient’s tumor, which would be more invasive. We also know that when a tumor that initially responds to treatment starts to grow again, it acquires new mutations and characteristics that make it resistant to the therapy to which it once responded. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time.

    • Neal J. Meropol, MD
    • Chief of hematology and oncology Case Western Reserve University School of Medicine and University Hospitals

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