Gene mutations in tumors affect radiation sensitivity

A new Northwestern Medicine study identifies common and rare gene mutations that impact radiation resistance and sensitivity, an important step toward providing more individualized and effective radiotherapy for patients with cancer.

Studying tumors from 27 different types of cancer, investigators profiled 92 genes with 400 unique mutations and determined the impact of these genes on radiation response.

They developed a computational algorithm that nominated mutations in genes that were likely to affect sensitivity to radiation. Scientists tested these mutations by placing them in several human cells and assessed their impact using high-volume arrayed phenotypic profiling.

Cancer genomics spurred 'silver bullet' drugs; radiotherapy is more complex

"Cancer genomics over the last decade has revolutionized how we treat cancer patients from a drug perspective," said Abazeed, also co-leader of the lung cancer program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "If you find the right mutation in a patient's tumor, there are now a host of drugs that can selectively target that mutation and, therefore, that tumor."

Abazeed and colleagues have tested different dosing of radiation therapy based on the mutation in "patient avatars," human tumors grown directly in mice.

"Our strategies appear to work in a subset of the targets we identified," Abazeed said. The next step will be a clinical trial testing different radiation doses or combinations of radiation with other drugs based on the genetic alterations of individual tumors.

The findings also reveal important insights into the interactions between the human genome and radiation as it relates to environmental radiation exposures.

Reference:

Dr. Mohamed Abazeed, et al,"The mutational landscape of cancer's vulnerability to ionizing radiation",Clinical Cancer Research