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Falchook Sheds Light on Rare Oncogenic Drivers in NSCLC

Angelica Welch
Published: Tuesday, Aug 28, 2018

Gerald S. Falchook, MD, MS

Gerald S. Falchook, MD, MS

Patients with mutations in NTRK, RET, MET, HER2, and KRAS G12C have limited therapeutic options, but potentially promising agents are on the horizon, said Gerald S. Falchook, MD, MS, adding that these rare oncogeneic drivers in non–small cell lung cancer (NSCLC) are beginning to be better understood.

State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Falchook, director of Drug Development of Sarah Cannon Research Institute at HealthONE, discussed these oncogenic drivers in advanced disease.

NTRK

There are 3 members in this family, Falchook explained—TRKA, TRKB, and TRKC. These are encoded by NTRK1, NTRK2, and NTRK3. TRK causes downstream activation of MAPK, PI3K, and PLCg pathways, which results in cell proliferation and increase cell survival and migration, leading to tumor growth.

In May 2018, the FDA granted a priority review to a new drug application for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors with an NTRK gene fusion.

RET

RET fusions are chromosomal rearrangements that create a fusion between RET and other proteins, activating the RET receptor as well as the MAPK and EGFR pathways. These fusions occur in about 2% of NSCLC cases—usually in patients younger than 60 years old who are never smokers or former light smokers with a poorly differentiated histology and early lymph node metastasis.
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