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Medical News Today, By Deep Shukla

Lung cancer is the second most commonly diagnosed cancer worldwide and the leading cause of cancer deaths. About 80–85% of all lung cancer cases belong to a category known as non-small cell lung cancer (NSCLC).

Alterations in the ROS-1 gene, a receptor tyrosine kinase often involved in genetic mutations in various forms of cancer, are present in a subset of NSCLC cases.

Drugs that inhibit the tyrosine kinase encoded by the ROS-1 protein are effective, but cancer cells tend to acquire resistance to these drugs.

Recently, results from the phase I/II TRIDENT-1 clinical trial suggest that a novel tyrosine kinase inhibitor (TKI), repotrectinib, shows antitumor activity in ROS-1-positive advanced non-small cell lung cancer patients, including those previously treated with other ROS-1 inhibitors. The findings have not yet been peer-reviewed or published.

Study author Byoung Chul Cho, Ph.D., a professor of oncology at the Yonsei Cancer Center in South Korea, told Medical News Today:

“In the TRIDENT-1 trial, repotrectinib demonstrated clinically meaningful benefit in TKI naive and TKI resistant advanced ROS-1 NSCLC. Trial results provide a strong rationale to use repotrectinib in TKI naive and TKI resistant ROS-1 NSCLC.”

Prof. Cho presented the results of the clinical trial in late October at the 34th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium on Molecular Targets and Cancer Research in Barcelona, Spain.

ROS-1 genes and tyrosine kinase inhibitors in lung cancer

Around 0.9-2.6% of non-small cell lung cancers involve an alteration of the ROS-1 gene.

The ROS-1 gene encodes an enzyme that belongs to the receptor tyrosine kinases family.

In healthy cells, the ROS-1 receptor tyrosine kinase is involved in several pathways associated with the growth, proliferation, and survival of cells.

Under certain circumstances, such as exposure to environmental factors that cause DNA damage, the part of the chromosome containing the ROS-1 gene can break off and fuse with another gene to form a fusion gene. The fusion of these genes can lead to the overexpression or upregulation of the activity of the hybrid ROS-1 enzyme, potentially resulting in the development of cancer.

Tyrosine kinase inhibitors (TKIs) such as crizotinib, ceritinib, and entrectinib that target the ROS-1 fusion protein have been effective in individuals with non-small cell lung cancers.

But cancer cells often acquire resistance to these therapies, thus highlighting the need for new treatments targeting the ROS-1 tyrosine kinase.

Repotrectinib is a new-generation drug that inhibits ROS-1 and other receptor tyrosine kinases, and results from in vitroassays suggest that repotrectinib is at least 90-fold more potent than crizotinib and entrectinib.