Colon and Pancreatic Trials Exemplify “Bench-to-Bedside” Research

One of the Ruesch Center’s most promising junior faculty members is hoping to reshape the way colorectal and pancreas cancers are treated.

Michael Pishvaian, MD, PhD, is not satisfied with the status quo when it comes to treatments for colon and pancreatic cancers — two of the most deadly cancers out there.

Michael Pishvaian at Georgetown LombardiDr. Michael Pishvaian thinks we need a new way forward in colon and pancreas cancer treatments.

That is why Pishvaian, assistant professor of oncology and hematology at Georgetown Lombardi Comprehensive Cancer Center, is working to chart a new course in research that resonates between the bench and bedside.

His research starts in the lab, where he works to understand what drives cancer cells, and he tests novel targeted therapies designed to block those critical pathways. Treatments that have shown promise in the lab are then integrated into clinical trials, designed to test these novel targeted agents in patients with cancer. However, his research also includes bringing tumor samples from patients on these trials back to the lab, to help understand how a tumor might be resistant to a promising therapy.

Pishvaian’s research objectives are exemplified by one ongoing trial and one planned translational project, both supported by the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown Lombardi Comprehensive Cancer Center.

“These studies are at the heart of the translational research that is needed to improve outcomes for patients with pancreas and colon cancers, and to tailor individualized therapies that move us toward a cure,” Pishvaian says.

The Problem of Chemotherapy Resistance
Compared to normal cells, colorectal and pancreas cancer cells possess a number of abnormalities, including DNA-repair deficiencies. These DNA-repair deficiencies normally cause cancer cells to be particularly sensitive to chemotherapeutic agents, which act by breaking DNA strands and disrupting cell proliferation.

Yet cancer cells can become resistant to this DNA strand-breaking process—and thus to chemotherapy—by relying on the activity of other DNA-repair enzymes, such as one called “PARP”.

Pishvaian seeks to fix this PARP-related resistance problem by combining a novel and promising inhibitor of PARP—called ABT-888—with routinely used DNA-damaging chemotherapy agents, such as oxaliplatin and fluorouracil, in patients with metastatic pancreas cancer. ABT-888 should diminish the DNA-repair capabilities of cancer cells, resulting in their enhanced death.

Moreover, Dr Pishvaian will assess the levels of a number of biomarkers that will help predict patient response to the therapy described above. He then hopes to apply ABT-888-based novel treatment combinations to patients with these predictive markers, thus dramatically increasing treatment response rates and ultimately patient survival.

“Molecularly-tailored Therapy”

In an upcoming project, Pishvaian and colleagues will launch a novel clinical trial that will evaluate patient pancreatic tumor response to “molecularly-tailored therapy.”

This entails analyzing tumor biopsies to assess the degree of expression of specific biomarkers, or proteins, which can help predict how individual patients will respond to certain chemotherapy treatments. The idea is that chemotherapy regimens for patients will then be selected based on these biomarker levels within their tumor samples.

“If this study provides enough data to validate the conduct of subsequent larger studies with this type of molecularly-tailored therapy, then the Ruesch Center will have made huge advances toward the goal of creating successful personalized medicine,” Pishvaian says.

For more information about these trials and other clinical research at the Ruesch Center and Georgetown Lombardi, please visit insert link