Trever Bivona, MD, PhD

Improving Personalized Treatment for Lung Cancer

“This is a watershed moment in the history of cancer treatment research,” says Trever Bivona, MD, PhD, recipient of this year’s American Lung Association Lung Cancer Discovery Award. A growing number of lung cancer patients are being treated with drugs that target the genetic cause of their lung cancer, known as personalized medicine. Yet while patients may respond quickly, they often become resistant to the treatment.

“This is a watershed moment in the history of cancer treatment research.”

Dr. Bivona’s research focuses on lung cancers that are associated with a particular mutation in a gene called EGFR. Patients with this type of lung cancer are treated with a drug called erlotinib (Tarceva), which blocks the mutant form of EGFR. While the treatment induces tumor regression, the cancers develop resistance to the drug. Dr. Bivona hopes to better understand how lung cancer becomes resistant to erlotinib.

When he analyzed potential genes that might be causing this resistance, using human lung cancer grown in the laboratory and also in mice, he and his team discovered that the most prominent gene involved was one called AXL. This gene is turned on and allows EGFR-mutant lung cancers to survive in the face of erlotinib treatment. He hopes to discover how AXL is turned on in the setting of erlotinib resistance and how AXL promotes erlotinib resistance in lung cancers.

AXL is a type of enzyme called a kinase. “It turns out this class of enzyme is a very good drug target. Kinases can be targeted with potent drugs, and there are a host of therapies that have emerged in the last few years that target kinases, but none of them are highly specific against AXL,” Dr. Bivona says. “Many drug companies have been working on developing new drugs targeting kinases, including AXL. That means we can move rapidly to test drugs that target AXL and potentially use them for clinical testing. This paves the way for very rapid clinical translation.”

He is collaborating with Dr. Kevan Shokat, a Howard Hughes Medical Institute Investigator and chair of the UCSF Department of Cellular and Molecular Pharmacology at the University of California, San Francisco to develop new drugs that target AXL.

“The American Lung Association grant will accelerate this line of investigation,” Dr. Bivona said. “Without this funding, it would be very difficult to go forward with testing drugs and moving the most promising ones toward the clinic. It’s a real catalyst.”