ATM kinase inhibitor combines with target therapies to wipe out cancer cells

While cancer therapies that target specific genes or disease pathways might prolong life span, they can also result in highly resistant tumors when tiny reservoirs of cancer cells survive therapy, develop, and spread.

A team headed by Duke Cancer Institute researchers uncovered a potential new technique to impair the repair process that cancer cells employ after treatment, blunting their capacity to regenerate, as part of their research for strategies to extend the life advantage of targeted therapies. The method might be used to develop a new therapeutic plan.

The results were published in the journal Science Translational Medicine on March 30^th.

There is a significant need to figure out ways to make targeted therapies work better with more long-lasting effect. This research provides a potential strategy to do that with drugs that are currently under investigation.”

Kris Wood, PhD, Study Senior Author and Associate Professor, Department of Pharmacology and Cancer Biology, Duke Cancer Institute

Targeted therapies, according to Wood and colleagues, cause breaks in the DNA strands of cancer cells that survive treatment. The ataxia telangiectasia mutated (ATM) enzyme is required for efficient DNA break repair, which is important for tumor cell viability.

We were surprised to find that the ATM pathway was frequently activated by these surviving cancer cells. That finding led to the next question: Could we disrupt the repair process?”

Kris Wood, PhD, Study Senior Author and Associate Professor, Department of Pharmacology and Cancer Biology, Duke Cancer Institute

ATM inhibitors, which are now under investigation, were utilized by the researchers, and the response was yes. Scientists discovered that an ATM kinase inhibitor, in association with targeted therapy, eliminated remaining cancer cells in non-small cell lung cancer mice models and laboratory cultures, resulting in more permanent cancer remission.

In real-life situations, there was more confirmation. When compared to patients who do not have an ATM mutation, patients with lung cancer who have an ATM mutation that reduces its function had a longer progression-free survival with targeted therapy.

Together, these findings establish a rationale for the mechanism-based integration of ATM inhibitors alongside existing targeted therapies.”

Kris Wood, PhD, Study Senior Author and Associate Professor, Department of Pharmacology and Cancer Biology, Duke Cancer Institute