Advances within the field of oncogenetics over the past several decades have ushered in a new stage in cancer treatment. Continued discoveries in the realm of gene fusions coupled with innovations in detection technology have since fueled development of targeted therapies. Data have increasingly shown the therapeutic potential of the neurotrophic tyrosine receptor kinase (NTRK) gene mutation as a target for inhibition. Preclinical and clinical studies of recently developed NTRK inhibitors have demonstrated robust response in NTRK-dependent tumors. Additionally, NTRK inhibitors have demonstrated activity in inhibiting anaplastic lymphoma kinase- (ALK) and proto-oncogene receptor kinase- (ROS1) dependent tumors. This supplement chronicles the evolving role of gene mutations within the cancer treatment spectrum, from discoveries in tumor biology and detection technologies, to the development targeted therapies and the clinical impact of pivotal trial data.
Tumor Biology and Treatment Approaches:
Decisions regarding cancer therapy have historically been based largely on histologic considerations. For example, lung cancers have typically been categorized into small-cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) types, the latter of which is then further subdivided into squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma.1 In the past, platinum-based doublet chemotherapy was the standard treatment for patients with advanced NSCLC; efficacy was limited.1 However, after a study demonstrated better response to pemetrexed than gemcitabine among patients with nonsquamous NSCLC,1 researchers began evaluating whether genetic variations of cancer have a role in treatment selection.
... to read the full story