Handbook of Targeted Cancer Therapy and Immunotherapy

91 transcription and further amplified by polymerase chain reaction (PCR) to allow for the detection of RNA sequences (15). The clinical utility of transcriptional profiling is evolv ing and is a component of tumor biology that should be taken into consideration in parallel with genomic profiling efforts. RNASeq is advantageous as it can allow for the detection of unique isoforms/splice variants, gene expression signatures, and fusions/rearrange ments (14). Differential gene expression in cancer pathways can have downstream effects that potentiate tumor growth, often without corresponding genomic alterations, which may highlight avenues for therapeutic intervention (16). In addition to gene expression signatures, RNASeq also can identify gene fusions and fusion transcript expression, which have prognostic, and diagnostic, implications and have been emerging as some of the most compelling therapeutic targets in preci sion oncology (16). Personalized Cancer Therapy Progress in the field of genomic medicine has profoundly improved our understanding of cancer biology and ushered in the era of precision oncology. NGS is now routinely performed at both academic and community cancer centers and can inform oncologists of which molecular char acteristics are driving a tumor that may have therapeutic relevance. Early successes in preci sion oncology are highlighted by the benefits of trastuzumab in HER2-positive breast cancer (17) and vemurafenib in BRAF V600E mutant melanoma (18), among others. A study from the MD Anderson Cancer Center identified that in a phase I setting, patients treated with molecularly matched therapies had an improved overall response rate (27%) in comparison to those who received non-matched therapies (5%) (19). The phase II MyPathway study investigated if U.S. Food and Drug Administration (FDA)-approved therapies had activity across 14 different tumor types, and identified meaningful responses in 23% of patients with metastatic solid tumors when matched with agents outside of their FDA-approved indications (20). These findings are promis ing for cancer therapeutics, though a remaining challenge is the lack of FDA-approved therapies for most alterations. Basket trials are a way to address this concern through a tumor-agnostic approach to enrollment, which can facilitate the evaluation of matched therapies in patients with less common alterations.

Copyright © 2023 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited.