Unlocking the Secret to Tumors’ Varying Radiation Vulnerability

A team including Cleveland Clinic researchers has identified a variety of genetic determinants that enable cancer cells to survive after exposure to radiation.

The groundbreaking research, which utilized a collection of 533 genetically profiled human tumor-derived cell lines, found that the cells’ sensitivity to ionizing radiation results from significant underlying biological diversity within and across lineages.

“Our team’s research helps explain why individual tumors can vary in their susceptibility to DNA-damaging radiation and drugs,” says Cleveland Clinic radiation oncologist Mohamed Abazeed, MD, PhD, the lead author of the study published in Nature Communications.

His collaborators included investigators at Cleveland Clinic, Case Western Reserve University, Korea’s Seoul National University College of Medicine, the Broad Institute at MIT and Harvard, the Dana-Farber Cancer Institute, Harvard University and the Howard Hughes Medical Institute.

The researchers showed that individual somatic copy number alterations, gene mutations and the expression of individual genes and gene sets correlated with cancer cells’ ability to survive radiation exposure.

Although these genetic determinants are diverse, their presence in multiple cancer types suggests that combinations of only a limited number of functionally relevant alterations can confer resistance to therapeutic radiation across cancer types.

Characterizing genetic factors that dictate cellular response to radiation is a fundamental step toward using biomarkers to predict individual cancer patients’ radiotherapy outcomes, and to tailoring radiation treatments to exploit the genetic alterations present in a patient’s tumor.

“The findings suggest that the promising tactics of personalized, genetically targeted cancer therapies can be extended to radiation therapy, and that we can develop predictive tools to guide clinical decision-making and patient selection,” Dr. Abazeed says.