Israeli researchers May Have Improved Therapy for Lung Cancer

Weizmann’s research team. Back row (l-r) Dr. Roni Oren, Anna Rudnitsky and Dr. Mirie Zerbib. Front row (l-r) Nitin Gupta, Prof. Yosef Yarden and Dr. Suvendu Giri

Researchers from the Weizmann Institute of Science in Israel said they have identified a biomarker that they say may one day enable a subgroup of lung cancer patients to benefit from relapse-free treatment.

Nonsmokers who develop lung cancer can be treated effectively with new drugs, they say, but their tumors refuse to surrender without a fight. The drugs stop working in the long term because the tumors acquire secondary mutations that allow them to evade the medications’ therapeutic effects.

The Weizmann Institute of Science researchers reported findings that may lead to relapse-free treatment for a sizeable subgroup of lung cancer patients. In a study in mice, the scientists have identified a biomarker that may help physicians select lung cancer patients who can be treated with a single antibody-based drug that is likely to bring about full remission, without cancer relapse.

Israeli high-tech firms and scientists have always been at the forefront of medical research and breakthroughs including cancer. Just a few weeks ago researchers from Tel Aviv University reported they destroyed 90% of the multiple myeloma blood cancer cells under laboratory conditions, and 60% in human tissues taken from patients at Rabin Medical Center (Belinson Hospital), using an RNA-based drug delivered to the cells by targeted lipid nanoparticles.

“We have found a potential biomarker that may change the way patients with lung cancer are treated worldwide,” says Prof. Yosef Yarden of Weizmann’s Immunology and Regenerative Biology Department, who led the study. “Similar to how the presence of BRCA mutations predicts how breast and ovarian cancer patients will respond to drugs, the new biomarker might make it possible to match some lung cancer patients with the specific medication most likely to help them.”

Most lung cancers are due to tobacco smoking, but the second-largest fraction of cases affects nonsmokers, and it’s characterized by mutations in a gene called EGFR. The current research began when Dr. Ilaria Marrocco, then a postdoctoral researcher in Yarden’s lab, reviewed the literature from clinical trials and realized that all patients with EGFR-positive lung cancer were being treated using the same multidrug protocol – regardless of which of the 30 known EGFR mutations were harbored in their individual tumors. These patients eventually developed drug resistance that led to cancer relapse. Marrocco wondered whether, by sorting lung tumors according to specific EGFR mutations, it might be possible to create a more personalized drug protocol and achieve better results.

“Dr. Marrocco’s observation inspired us to search for a biomarker that would predict which patients would respond well to therapy, according to the specific mutations they carry,” says Yarden. The scientists decided to focus on one of the two most common gene variants associated with EGFR in lung cancer: the L858R mutation, in which a single amino acid, out of several hundred, is replaced with another one, at point 858 in EGFR. This mutation occurs in about 40 percent of lung cancer patients whose tumors are characterized by EGFR mutations.

The new study also explains why previous attempts to treat EGFR-mutated lung cancer with Erbitux had failed or, at best, produced conflicting results. Explains Yarden: “Since new EGFR inhibitors were approved as lung cancer drugs nearly 10 years ago, all patients now receive these anti-EGFR medications, irrespective of the identity and number of their EGFR mutations. They are highly effective for a while, but they permit the emergence of secondary mutations that accelerate cancer relapse. By the time Erbitux is given, it is usually ineffective because it can work only against certain EGFR mutations. Our study demonstrates the importance of preselecting lung cancer patients who can be effectively treated with Erbitux from the start, based on their mutation profile.”

The scientists say that the next step would be to launch a clinical trial to establish the effectiveness of this treatment for human lung cancer patients, something that will be made easier by the fact that Erbitux has already been approved for treating other cancer types. In the meantime, Yarden and Marrocco are excited about the potential for their research to eventually have an impact on clinical practice. Marrocco: “The L858R biomarker could help save lives by offering physicians a way to provide personalized drug treatment for lung cancer patients who carry the relevant mutation.”