The Molecular Pharmacology Program focuses on uncovering pathways that drive tumor progression and identifying novel therapeutic targets. We bridge basic science with translational research by studying mechanisms like anaphase catastrophe and exploring retinoic acid receptors and USP18. The program's work on targeting vulnerabilities in aneuploid cancer cells and collaborations with external partners integrate laboratory discoveries with population health studies, advancing our understanding of cancer biology and treatment.
The program also addresses clinical challenges by investigating combination therapies and systemic factors like glycemic control in lung cancer patients. Our studies highlight the potential of precision oncology and inform strategies to improve treatment outcomes and reduce health disparities. By integrating foundational discoveries with clinical applications, the Molecular Pharmacology Program significantly contributes to advancing cancer research and developing impactful therapies.
Targeting aneuploid cancer cells
The Molecular Pharmacology Program investigates how certain cancer cells become vulnerable due to having extra chromosomes (aneuploidy) and aims to use that weakness against them. One key discovery, called “anaphase catastrophe,” is a process that causes these abnormal cells to die without harming normal ones. This approach has shown promise in various cancers, including those of the colon, lung, and pancreas—even when common cancer mutations are present.
Building on this, the team found that blocking Cyclin-dependent Kinase 2 (CDK2) can trigger anaphase catastrophe. While this kills many cancer cells, some cells survive by becoming even larger and more abnormal. To address this, the team is testing combinations of CDK2 blockers with other drugs that interfere with cancer cell division. Early results suggest that these combinations may wipe out resistant cells and improve outcomes for patients with hard-to-treat tumors.
Latest publications
Protein degradation pathway as cancer target
The Molecular Pharmacology Program’s research on USP18, a protein that supports cancer growth, has shown its strong influence on lung cancer survival and spread. By helping stabilize certain proteins and affecting how cells process fats, USP18 fuels tumor growth and metastasis. High USP18 levels in lung cancer patients also correlate with poorer outcomes.
In response, the team is developing drugs that block USP18’s effects. Early tests of three experimental compounds have slowed lung cancer cell growth and promoted cell death, though high USP18 levels reduce their impact. Current efforts focus on improving these inhibitors to create more effective therapies against lung cancer’s progression.
Taking aim at immune checkpoint resistance with novel retinoids
The Molecular Pharmacology Program is improving lung cancer immunotherapy by testing a new compound called IRX4647, which works with existing immune “checkpoint” treatments. In preclinical studies, combining IRX4647 with an anti-PD-L1 therapy slowed tumor growth, attracted more immune cells, and increased helpful immune signals. Unlike therapies that target cancer cells directly, IRX4647 strengthens the body’s own defenses against cancer. These promising results lay the groundwork for future clinical trials and may help patients whose tumors resist current immunotherapies.
Metabolic syndromes in lung cancer survival
Our research shows that controlling conditions like diabetes and obesity can help people with lung cancer live longer. Working with institutions including University of Texas MD Anderson Cancer Center, Louisiana State University, and Georgetown University, we analyzed large patient datasets to see how factors like blood sugar control and body mass index affect survival. We found that better-managed blood sugar levels improve outcomes, regardless of a patient’s cancer stage or smoking history.
These results suggest a focus on metabolic health could enhance lung cancer treatment strategies. They also set the stage for future studies to confirm these findings in broader patient groups.