Combination drug therapy overcomes drug-resistant lung cancer in the lab

UC San Francisco scientists recently demonstrated the effectiveness of a combination drug therapy that halts the growth of drug-resistant lung cancer cells in the lab. The finding promises to improve standard treatments for lung cancer, which often lose their effectiveness in patients after less than two years.

Physicians have long sought to treat cancer by blocking the signals that promote tumor growth. In many cases, however, cancer cells develop resistance to these treatments.

A research team led by Sourav Bandyopadhyay, PhD, discovered that lung cancer cells continued to grow in the presence of these drugs because the cells were using an alternative signaling pathway. The study, published on November 26, 2018 in the journal Nature Medicine, also found that the resistance could be thwarted with the addition of a second drug that blocked these alternative signals.

Bandyopadhyay is a faculty member in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine. He is also a member of the UCSF Helen Diller Family Comprehensive Cancer Center and the Quantitative Biosciences Institute.

UCSF School of Pharmacy

Sourav Bandyopadhyay, PhD, senior author on the paper, showed that a combination of drug treatments could be used to halt the growth of lung cancer cells in the lab.

To make the discovery, researchers used lab cell lines to model a common category of lung cancers, which are caused by mutations to a gene called epidermal growth factor receptor (EGFR). Mutations to EGFR can cause tumors to grow rapidly, but drugs that block EGFR tend to lose their effectiveness over time.

The research team treated these cancer cell lines with EGFR inhibitors and isolated those that survived. These drug-resistant cells were then tested against a panel of 94 additional drugs. The team found that drugs that blocked an enzyme called Aurora kinase halted cancer cell growth when administered alongside traditional EGFR inhibitors.

Intriguingly, six months ago the Bandyopadhyay lab showed that an unrelated group of drug-resistant breast cancers could also be successfully treated by adding Aurora kinase-targeting drugs to existing therapies.

“Our studies suggest that distinct cancers may follow common or convergent biological pathways to achieve drug resistance,” said Bandyopadhyay. “If true, this observation may lead to the development of therapies that can overcome drug resistance in cancer more generally.”