A Novel Approach to Attacking Gastric Cancer

A $100,000 grant is helping Sylvester researchers identify FDA-approved drugs that can target immunotherapy-resistant tumors.

By Zeth Leon

Article Summary

• A project by Zheng Chen, M.D., Ph.D., an assistant professor of surgical oncology, received a $100,000 grant from the DeGregorio Family Foundation.

• Dr. Chen will analyze the expression of immune cell markers and druggable​ targets in tissue samples from gastric adenocarcinoma.

• The project will then evaluate the therapeutic efficacy of the top three FDA-approved drugs that target the most highly expressed proteins associated with immune suppression in gastric cancer.

Gastric cancer, also known as stomach cancer, is one of the most lethal types of cancer, with a five-year survival rate in the U.S. of around 32%. Globally, it has the fifth-highest rates of both incidence and mortality. Among the barriers to improving the survival rate is that only around 30% of patients respond to immune checkpoint therapy alone or in combination with standard chemotherapy, which is designed to help the body recognize cancer cells so the immune system can attack them. 

A researcher at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, hopes to change those numbers through a novel approach: using FDA-approved drugs to overcome the resistance of certain gastric tumors to immunotherapy. Zheng Chen, M.D., Ph.D., an assistant professor of surgical oncology who specializes in gastric and esophageal cancer, received support for his work through a new grant from the DeGregorio Family Foundation for gastric and esophageal cancer research and the Torrey Coast Foundation.

The $100,000 Michael F. Price Memorial Grant from the foundation will be used to analyze the expression of immune cell markers and druggable​ targets in tissue samples from gastric adenocarcinomas. The goal is to pinpoint the top three proteins or targets most strongly associated with tumors that are resistant to immunotherapy treatments, then see which FDA-approved drugs have the highest potential for clinical impact in these tumors.

“We don’t need to generate any drugs. We don’t need to wait for any trials. It’s already on the market,” said Dr. Chen.

If successful, Dr. Chen’s research could accelerate new treatment strategies for a disease that continues to claim far too many lives.

A cancer research approach that integrates molecular, functional and translational science

In earlier research, Dr. Chen identified 29 potential genes that FDA-approved drugs could target in the immune desert phenotype of gastric cancer. One of three immune phenotypes of gastric cancer, the immune desert type has very few or no immune cells infiltrating to the cancer cells. As a result, the body’s immune system doesn’t recognize or attack the tumor effectively and it is very resistant to immunotherapy treatments. These 29 genes will be at the center of this new project.

Funding from the DeGregorio Family Foundation will support the first aim of this project: to utilize cytometry by time of flight (CyTOF) technology to examine the expression of immune markers and druggable targets in 150 gastric cancer tissue samples. CyTOF is a mass spectrometry technique used for studying immune cell activation and function by analyzing single cells and measuring many cellular parameters at once.

Dr. Chen’s lab will also employ CyTOF on tissue microarrays derived from 56 gastroesophageal cancer patients treated with immune checkpoint blockade (a type of immunotherapy), including patients who responded to the therapy and those who did not.

 The rich number of variables in the data generated through CyTOF analysis will guide Dr. Chen’s selection of FDA-approved drugs with the greatest potential for clinical effectiveness in targeting immune-resistant tumors.

The second aim of this project is to evaluate the therapeutic efficacy of the top three FDA-approved drugs that target the most highly expressed candidate genes, both individually and in combination with immune checkpoint blockade therapy.

Rapid translation of insights from research to cancer care

Dr. Chen hopes to discover clinically significant druggable targets and assess their therapeutic effectiveness in preclinical models. Using spatial CyTOF staining, Dr. Chen’s team will identify molecular markers that predict how patients respond to combination therapies, speeding up the creation of tailored treatment plans.

 By prioritizing FDA-approved drugs, Dr. Chen and his team intend to rapidly translate these insights into clinical use, providing new hope for gastric cancer patients who do not benefit from existing therapies.

Potential applications for other types of cancer

While Dr. Chen’s research currently focuses on upper gastrointestinal cancers, including gastric and esophageal cancers, he sees potential for this new approach to be used to treat other cancers as well.

“We’re inventing a way to discover the weakness of cancers with a few immune cell infiltrations,” said Dr. Chen. “We think if our research is working and successful, maybe we can do similar things on other cancers by discovering different markers and targets.”

Tackling the devastation of gastric cancer

Dr. Chen, a native of China, has witnessed firsthand the effects of gastric cancer.

“When I was in China, I used to be a gastric cancer surgeon, and I touched gastric cancer patients, examined them and talked to them and their families, so I feel the pain of the patient because you cannot cure everyone,” said  Dr. Chen. “There are some in the clinic that you can operate on, but for many of them, it becomes too late. Surgery helps people today, but research is helping people in the future.”

 At Sylvester, Dr. Chen is focused on research. “Research is still our best choice to improve the clinical outcome,” he said. “So, the motivation is that our research helps treat and improve the clinical outcome and reduce the pain of the patients and their families. That’s why I want to thank all the foundations and organizations for giving funding to our research. [It] can transform into great things that people never could’ve imagined. I also want to express my deep gratitude to all the cancer patients who participate in research, as their willingness to contribute is invaluable in advancing cancer treatments and improving outcomes for future patients.”

“We don’t need to generate any drugs. We don’t need to wait for any trials. [The drugs are] already on the market.”

“We’re inventing a way to discover the weakness of cancers with a few immune cell infiltrations.”