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Importance of ROS1 gene fusions in non-small cell lung cancer

Cancer Drug Resistance 2023年第2期6卷 332-344页

作者： Meri Muminovic Carlos Rodrigo Carracedo Uribe andres alvarez-pinzon Khine Shan Luis E.Raez Department of Hematology-Oncology Memorial Cancer Institute/Memorial Health Care SystemFlorida International UniversityPembroke PinesFL 33028USA Department of Internal Medicine Memorial Health Care SystemFlorida International UniversityPembroke PinesFL 33028USA Office of Human Research Memorial Healthcare SystemPembroke PinesFL 33028USA

Targeted therapy has become one of the standards of care for advanced lung cancer.More than 10 genetic aberrations have been discovered that are actionable and several tyrosine kinase inhibitors(TKIs)have been approved to target each of them.Among several genetic aberrations that are actionable in non-small cell lung cancer(NSCLC),ROS1 translocations also known as gene fusion proteins,are found in only 1%-2%of the patient population.ROS1 mutations can usually be detected using a combination of techniques such as immunohistochemistry(IHC),Fluorescence in-situ testing(FISH),polymerase chain reaction(PCR),and nextgeneration sequencing(NGS).However,RNA NGS and ctDNA NGS(liquid biopsies)also contribute to the diagnosis.There are currently numerous FDA-approved agents for these tumors,including crizotinib and entrectinib;however,there is in-vitro sensitivity data and clinical data documenting responses to ceritinib and lorlatinib.Clinical responses and survival rates with these agents are frequently among the best compared to other TKIs with genetic aberrations;however,intrinsic or extrinsic mechanisms of resistance may develop,necessitating research for alternative treatment modalities.To combat the mechanisms of resistance,novel agents such as repotrectenib,cabozantinib,talotrectinib,and others are being developed.In this article,we examine the literature pertaining to patients with ROS1 tumors,including epidemiology,clinical outcomes,resistance mechanisms,and treatment options.

关键词： ROS1 targeted therapy non-small cell lung cancer

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