With new grant funding, researcher hopes to take down multiple causes of lung cancer with a single strike

A scientist at VCU Massey Comprehensive Cancer Center was awarded more than $2.7 million in grant funding to evaluate the effectiveness of a new targeted drug in treating the most common type of lung cancer.

Lung cancer is the leading cause of cancer death in the U.S., where approximately 80-85% of those tumors are classified as non-small cell lung cancer (NSCLC), according to the American Cancer Society.

Through a five-year R01 grant from the National Cancer Institute, Yuesheng Zhang, M.D., Ph.D., the Harrigan, Haw, Luck Families Chair in Cancer Research and a member of the Developmental Therapeutics research program at Massey, will use an innovative protein-based therapy to thwart the activity of two tumor-feeding genes — EGFR and HER2 — at the same time, as well as their cancer-related mutations.

“This advanced approach is kind of like using a single bullet to take down multiple cellular targets,” said Zhang, who is also a professor in VCU School of Medicine’s Department of Pharmacology and Toxicology at the VCU School of Medicine. “Promising results from this research could lay the groundwork for the clinical development of a new drug to treat NSCLC patients.”

The EGFR gene is a known driver of cancer. Its presence is often abundant or mutated in lung tumors. A class of therapies known as EGFR inhibitors has been a clinically effective treatment option for NSCLC by targeting the EGFR protein to hamper cancer cell growth. However, resistance to these therapies is common.

“Drug resistance in NSCLC remains a major clinical problem,” Zhang said. “Our objective through this grant-funded initiative is to investigate a new treatment that can overcome that resistance.”

Previous research led by Zhang revealed that a protein-based combination therapy was successful in overcoming tumor resistance to colorectal cancer treatment. Now, Zhang intends to test part of that same combination treatment, a genetically engineered protein therapy called PEPD-G278D, in preclinical lung models as well.

So far, Zhang and his team have found that PEPD-G278D causes the breakdown of EGFR, its genetic relative HER2 and the two receptors’ cancer-associated mutants — all known contributors to the development of cancer drug resistance — by binding to the receptors on the outer membranes of lung cancer cells.

Additionally, the researchers observed this new drug strongly suppresses NSCLC cell function and tumors resistant to current EGFR inhibitors.

Through this five-year project, Zhang aims to determine whether this treatment is more effective than the current standard of care options for NSCLC. The results of the research, Zhang hopes, will generate enough evidence to move the drug forward into lung cancer clinical trials.

Collaborators on this grant-funded research include Shawn Wang, Ph.D., co-leader of the Developmental Therapeutics research program at Massey; Nolan Wages, Ph.D., member of the Developmental Therapeutics research program at Massey; Lu Yang, Ph.D., of the VCU School of Medicine; and Boyko Atanassov, Ph.D., of Roswell Park Comprehensive Cancer Center.