Jamming the Lung Cancer Revolving Door

Lung cancer resistance narrowed to AXL protein

(RxWiki News) One of the unfortunate aspects of lung cancer is that it tends to have a high rate of recurrence. It can be treated successfully only to return, and that return often comes far too soon.

Scientists have discovered that the protein AXL can cause the body to become resistant to the commonly used lung cancer chemotherapy drug, Tarceva (erlotinib).

Knowing this may help find ways to block this protein so lung cancer treatments can become more effective.

"If you're a smoker, talk to your doctor about lung cancer screening."

Researchers at the University of California, San Francisco's Helen Diller Family Comprehensive Cancer Center, led by Trever Bivona, MD, PhD, uncovered this protein's menacing role.

"If we block AXL activation in the laboratory, we can overcome resistance to Tarceva," said Dr. Bivona, an assistant professor of hematology and oncology. "This paves the way for novel and more effective therapies."

Dr. Bivona and his colleagues are working with Kevan Shokat, PhD, chair of the UCSF Department of Cellular and Molecular Pharmacology, to develop drugs for clinical testing that will block AXL activity. 

Treating lung cancer generally involves some mixture of surgery, radiation therapy and chemotherapy. Often, all three therapies are used.

Erlotinib is a chemotherapy medication that works by targeting and blocking a particular enzyme called the epidermal growth factor receptor (EGFR).

AXL gets into the action by "rescuing" lung cancers from the EGFR treatment, according to the authors.

The molecule AXL is known as a kinase, which will be used as a target for new drug design. Incidentally, Tarceva - along with many other targeted cancer drugs - blocks kinases of some sort.

Findings from this study were published in the July 1 issue of Nature Genetics.

This research was funded by grants or award monies from the National Institutes of Health, Uniting Against Lung Cancer Research, National Lung Cancer Partnership, La Caixa Foundation, American Cancer Society and a Korean Health Technology R&D Project.

No financial conflicts of interest were declared.

Review Date: 
July 5, 2012