Therapeutical Options in ROS1-Rearranged Advanced Non Small Cell Lung Cancer

• Published in: International journal of molecular sciences Vol. 24; no. 14; p. 11495
• Main Authors: Stanzione, Brigida, Del Conte, Alessandro, Bertoli, Elisa, De Carlo, Elisa, Revelant, Alberto, Spina, Michele, Bearz, Alessandra
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.07.2023; MDPI
• Subjects: Antimitotic agents; Antineoplastic agents; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Chemotherapy; Crizotinib - therapeutic use; Development and progression; Gene Rearrangement; Genes; Health aspects; Histology; Humans; Kinases; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical prognosis; Metastasis; Mutation; non small cell lung cancer; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Response rates; Review; ROS1; target therapy; Tumors; Tyrosine; non small cell lung cancer; ROS1; target therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241411495

ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9-2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI). Crizotinib, a first-generation TKI, was the first target-therapy approved for the first-line treatment of ROS1-positive NSCLC. Recently, entrectinib, a multitarget inhibitor with an anti-ROS1 activity 40 times more potent than crizotinib and better activity on the central nervous system (CNS), received approval for treatment-naive patients. After a median time-to-progression of 5.5-20 months, resistance mechanisms can occur, leading to tumor progression. Therefore, newer generation TKI with greater potency and brain penetration have been developed and are currently under investigation. This review summarizes the current knowledge on clinicopathological characteristics of ROS1-positive NSCLC and its therapeutic options.