Titles and Affiliations
Professor and Chair of the Department of Radiation Oncology
Research Area
Testing whether CDK2 inhibitors can boost the impact of radiation therapy in aggressive breast cancers.
Impact
Radiation is highly effective in many breast cancers. But patients with high-risk disease, like triple-negative or estrogen receptor (ER)-positive cancers with extensive lymph node involvement, still face high recurrence rates. CDK2 inhibitors are a new class of drugs that block cancer cells from dividing and repairing damage, making them more vulnerable to treatment. By pairing radiation with CDK2 inhibitors, Dr. Speers hopes to enhance tumor cell killing and stimulate the immune system. This dual approach could lead to more durable responses, offering new treatment strategies for patients with limited options.
Progress Thus Far
Dr. Speers and his team tested two CDK2 inhibitors, tagtociclib and INX-315, across multiple breast cancer laboratory models to determine effective doses for combining with radiation. Early experiments showed that CDK2 inhibition can make certain models more sensitive to radiation, and the team has begun studying whether this combination increases DNA damage, disrupts the cell’s ability to repair that damage, and activates immune signaling pathways that could make tumors more visible to the immune system. In a related line of work, the team found that targeting a different cell-cycle protein, Aurora kinase B, can also make triple-negative breast cancer models more sensitive to radiation while activating a key immune signaling pathway.
What’s Next
Dr. Speers and his team will identify which breast cancer models respond best to the combination of CDK2 inhibitors and radiation and investigate why. They will study whether CDK2 inhibition blocks DNA repair, increases abnormal DNA fragments capable of activating immune pathways, and triggers a key antiviral immune signaling program known to play a role in anti-tumor immune responses. These studies aim to lay the groundwork for clinical trials that combine radiation with CDK2 inhibitors, with the goal of delivering more effective treatments for patients with aggressive breast cancer.
Biography
Corey Speers, MD, PhD is the Merle M. Salter Endowed Professor and Chair of the Department of Radiation Oncology at the University of Alabama at Birmingham Heersink School of Medicine. Dr. Speers’ research focuses on understanding and exploiting the therapeutic vulnerabilities of aggressive forms of breast cancer, including triple-negative and inflammatory breast cancer. His laboratory leads a broad translational research program spanning basic mechanistic studies, preclinical modeling, and early-phase clinical trials. Dr. Speers is a national expert in developing radio sensitizing strategies that pair radiation with targeted agents such as PARP inhibitors, CDK4/6 inhibitors, and androgen receptor antagonists. His team has pioneered genomic signatures—POLAR and ARTIC—that are the first predictive biomarkers of radiation benefit in breast cancer, now being validated for clinical use.
Dr. Speers earned his MD and PhD through the Medical Scientist Training Program at Baylor College of Medicine and MD Anderson Cancer Center, followed by residency and Holman Pathway training at the University of Michigan, where he served on faculty for nearly a decade. He has authored over 150 peer-reviewed publications, holds four patents, and is co-founder of PFS Genomics, recently acquired by Exact Sciences. A committed collaborator and mentor, Dr. Speers works closely with multidisciplinary teams to advance precision radiation oncology.
