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- Title
NGS Testing Helps to Identify New Treatment Opportunities for Advanced Solid Tumor Cancers Driven by Molecular Alterations.
- Authors
Thacker, Audrey; Templer, Jessica; Magharyous, Hany; Multani, Pratik; Christiansen, Jason; Lamoureux, Jennifer
- Abstract
NTRK, ROS1, ALK and RET fusions have been identified as oncogenic drivers in multiple solid tumors. In general, these gene alterations are rare, but targeted therapies are being developed that may provide new therapeutic options for patients whose tumors harbor these alterations. However, in order to develop these new drugs, new methods must also be developed to efficiently and comprehensively identify appropriate patients. Two clinical stage investigational small molecule tyrosine kinase inhibitors, entrectinib (RXDX-101) and RXDX-105, target TRK/ROS1/ALK and RET, respectively. The anti-tumor effects of entrectinib and RXDX-105 have been demonstrated in multiple preclinical models, including in cell lines and in murine patient-derived tumor models, driven by NTRK, ROS1, ALK or RET fusions. Entrectinib and RXDX-105 exerted these potent inhibitory effects, in vitro and in vivo, in cancer models driven by NTRK, ROS1, ALK or RET alterations, irrespective of their histologies. Based upon these data, clinical trials are underway to study these two investigational agents and determine their safety and efficacy in molecularly selected patients. Patients with solid tumors containing NTRK, ROS1 or ALK fusions are being enrolled in the ongoing STARTRK-2 trial of entrectinib (NCT02568267) and patients with RET fusions are being enrolled in the ongoing Phase1/1b RXDX-105-01 trial of RXDX-105 (NCT01877811). To date, both entrectinib and RXDX-105 have demonstrated durable RECIST responses in a high proportion of molecularly selected patients. Utilization of Next Generation Sequencing testing for alterations in NTRK, ROS1, ALK and RET has proven to be a valuable tool in selecting patients with solid tumor malignancies, for whom promising new treatment opportunities (such as entrectinib and RXDX-105) are being developed.
- Publication
Clinical Laboratory Science, 2017, Vol 31, Issue 3, p167
- ISSN
0894-959X
- Publication type
Academic Journal