A Novel Approach to Attacking Gastric Cancer – Sylvester Comprehensive Cancer Center

Sylvester Comprehensive Cancer Center shared a post on LinkedIn:

“A $100,000 Grant is Helping Sylvester Researchers Identify FDA-Approved Drugs for Immunotherapy-Resistant Tumors.

By Zeth Leon

Article Summary:

• A project by Zheng Chen., 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 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: A Lethal Challenge

“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 survival rates is that only around 30% of patients respond to immune checkpoint therapy, either 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 Novel Research Approach at Sylvester Comprehensive Cancer Center:

“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 resistant to immunotherapy treatments, then determine 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.”

Integrating 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. This immune phenotype has very few or no immune cells infiltrating cancer cells, preventing the immune system from recognizing or attacking the tumor, making it highly resistant to immunotherapy. These 29 genes will be the focus of this new project.”

• The first aim of this project, supported by the DeGregorio Family Foundation, is to use cytometry by time of flight (CyTOF) to examine the expression of immune markers and druggable targets in 150 gastric cancer tissue samples.
• CyTOF, a mass spectrometry technique, analyzes immune cell activation and function by measuring multiple cellular parameters at once.
• The lab will also apply CyTOF to tissue microarrays derived from 56 gastroesophageal cancer patients treated with immune checkpoint blockade therapy to compare responders and non-responders.
• The data generated through CyTOF analysis will guide the selection of FDA-approved drugs with the greatest potential for targeting immune-resistant tumors.

Evaluating FDA-Approved Drugs for Gastric Cancer Treatment:

“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.”

Translating Research Insights to Cancer Care:

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

“By prioritizing FDA-approved drugs, Dr. Chen and his team aim 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 Cancers:

“While Dr. Chen’s research currently focuses on upper gastrointestinal cancers, including gastric and esophageal cancers, he sees potential for this approach to be used in other types of cancer.”

“We’re inventing a way to discover the weakness of cancers with a few immune cell infiltrations,” said Dr. Chen. “If our research is successful, we may be able to apply this method to other cancers by identifying different markers and targets.”

Addressing the Devastation of Gastric Cancer:

“Dr. Chen, a native of China, has witnessed firsthand the impact of gastric cancer.”

“When I was in China, I used to be a gastric cancer surgeon. I touched gastric cancer patients, examined them, and talked to them and their families. 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, it becomes too late. Surgery helps people today, but research helps people in the future.”

“At Sylvester, Dr. Chen is focused on research. “Research is still our best choice to improve clinical outcomes,” he said. “The motivation is that our research helps treat and improve clinical outcomes and reduce the pain of patients and their families. That’s why I want to thank all the foundations and organizations for funding our research. Their support can transform into great things that people never could have 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.”