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Israelis find biomarker for possible relapse-free lung cancer treatment

Researchers at the Weizmann Institute of Science spotlighted the EGFR gene.

The Weizmann Institute research team. Rear, from left: Dr. Roni Oren, Anna Rudnitsky and Dr. Mirie Zerbib. Front, from left: Nitin Gupta, Prof. Yosef Yarden and Dr. Suvendu Giri. Credit: The Weizmann Institute.
The Weizmann Institute research team. Rear, from left: Dr. Roni Oren, Anna Rudnitsky and Dr. Mirie Zerbib. Front, from left: Nitin Gupta, Prof. Yosef Yarden and Dr. Suvendu Giri. Credit: The Weizmann Institute.

Israeli researchers have identified a biomarker that might revolutionize lung cancer treatment.

A Weizmann Institute of Science study’s findings introduce a new avenue for personalized medicine that could lead to relapse-free treatment for certain lung cancer patients.

Common treatments for lung cancer include operations to remove tumors or portions of the lung, radiation therapy, chemotherapy and immunotherapy, which take a toll on the body. Newer medications have varying degrees of effectiveness, but long-term success has been elusive because the cancerous tumors develop secondary mutations that enable them to resist therapy.

While most lung cancer is due to tobacco smoking, the next largest cause—one that affects nonsmokers—is characterized by mutations in a gene called EGFR.

The study, led by Professor Yosef Yarden of Weizmann’s Immunology and Regenerative Biology Department, that may allow physicians to identify lung cancer patients who are suitable candidates for a singular antibody-based drug. This drug could potentially induce full remission without the threat of relapse.

The study was published in the peer-reviewed Cell Reports Medicine on Tuesday.

The team’s key breakthrough came when Dr. Ilaria Marrocco, a former postdoctoral researcher in Yarden’s lab, noticed a commonality among patients with EGFR-positive lung cancer: They were all treated with a standard multidrug protocol, regardless of the specific EGFR mutations in their tumors. This approach inevitably led to drug resistance and cancer relapse.

This observation prompted the researchers to seek a biomarker that could predict patient responses based on their unique EGFR mutations.

Their attention turned to the L858R mutation that affects approximately 40% of EGFR-mutated lung cancer patients. This mutation influences EGFR function in a distinct manner, causing receptors to pair up in the cancer cell membrane. Without this pairing, signals crucial for cellular replication are disrupted, preventing tumor growth.

To test this concept, the scientists used an antibody drug called cetuximab (Erbitux), which blocks the receptor pairing. In a mouse model with the L858R mutation, tumors regressed and didn’t reappear even after an extended period. This finding suggests that for patients with this mutation, a single drug might offer a path to complete recovery without relapse.

The findings also shed light on why previous attempts to treat EGFR-mutated lung cancer with Erbitux failed. By preselecting patients with the L858R mutation, therapy could be effectively tailored to their specific mutation profile, possibly preventing the emergence of secondary mutations.

The researchers are now preparing for a clinical trial to validate the treatment’s effectiveness in humans, leveraging Erbitux’s existing approval for other cancer types. This discovery could reshape clinical practices and offer hope for lung cancer patients carrying the relevant mutation.

Collaborating in the study were researchers from Italy and Japan.

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