A drug combination discovered by the UT Southwestern Simmons Cancer Center may extend the effectiveness of a lung cancer treatment and make it available to many more patients.
The findings, published in Nature Cancer, focused on epidermal growth factor receptor, EGFR, a protein that has a prominent role in the growth and survival of cancer cells, and resistance that builds up against inhibitors used to battle it. The researchers found that adding an interferon blocker, normally used to treat lupus, effectively wiped out this resistance in mice.
“This could be very important because it could expand the reach of the drug from about 15% to the majority of patients with lung cancer. That’s millions of people worldwide,” Amyn Habib, associate professor of Neurology and Neurotherapeutics at UT Southwestern Medical Center, a member of the Harold C. Simmons Comprehensive Cancer Center, and a staff physician at the Dallas Veterans Affairs Medical Center, said in a statement.
About 15% of lung cancer patients have a mutation in EGFR that makes it more active.
Habib’s lab discovered that the signaling pathways release interferons that resist the EGFR inhibitor. It was an unexpected finding because oncologists normally see interferons as allies in fighting cancer.
Their broad search included drugs outside of cancer treatment and found an interferon blocker used in lupus patients called anifrolumab. The researchers used anifrolumab to block interferons in mice, crippling the signaling pathway and wiping out the resistance to the EGFR blocker.
They also found that patients who did not have mutated EGFR also increased their interferon levels in response to EGFR inhibitors. This has kept those patients from responding to the EGFR inhibitor drugs. If the lupus drug could block the interferons, it would also open those patients up to the benefits of the EGFR blocking drugs.
Habib’s lab made the discovery by focusing on about 3,000 genes in the lung cancer cell and charting that were turned on or off. The data clearly led the researchers to increased activity with interferons.
This was previously unknown to medical science, and it is significant because EGFR signaling plays a role in other cancers including breast cancer and glioblastoma. Habib says his next step is to pursue clinical trials in lung cancer patients.
Other authors of the study from UT Southwestern are Ke Gong, Gao Guo, Nishah Panchani, Matthew Bender, David E. Gerber, John D. Minna, Farjana Fattah, Boning Gao, Michael Peyton, Kemp Kernstine, Cheng-Ming Chiang, Adwait Amod Sathe, Chao Xing, and Esra A. Akbay. Authors from other institutions are Kathryn H. Dao of Baylor Research Institute in Dallas, Dawen Zhao of Wake Forest School of Medicine in Winston-Salem, North Carolina, and Sandeep Burma and Bipasha Mukherjee, both at the University of Texas Health Science Center at San Antonio.
