Year: 2017
Type: article
Abstract: Over the past 15 years, we have seen a dramatic shift in the delivery of clinical care in oncology.The profound impact of trastuzumab in treatment of HER2-amplified breast cancer and of imatinib in chronic myeloid leukemia harboring the BCR-ABL translocation sparked intensive efforts to reproduce these early successes by targeting therapy to a tumor's individual molecular profile.This increased focus on precision medicine has grown in parallel with exponential improvements in the sequencing technologies used to decipher the cancer genome.Highthroughput next-generation sequencing (NGS) has made it possible to rapidly and accurately detect all classes of genomic alterations in tumors, including sequence mutations, copy number alterations, and structural rearrangements in hundreds or even thousands of genes simultaneously [1-3].As the sophistication of testing has improved, sharp declines in cost have facilitated access in the clinic.The appeal of large gene panels has been driven by the operational efficiencies afforded by running one standardized assay instead of multiple single analyte or customized gene panels, improved sensitivity compared to traditional methodologies, and the desire to detect rare and potentially actionable genomic variants across cancer types [3].Broad NGS can also provide additional clinically important information such as identification of microsatellite instability (MSI) and hypermutation, acquired resistance mutations, and, in assays utilizing paired germline sequencing, the presence of cancer predisposition alleles [4][5][6].This convergence of factors is expected ultimately to make NGS more cost-effective than performing multiple parallel tests.Tumor sequencing is already used to guide routine treatment decisions in many cancers including non-small cell lung cancer, melanoma, colorectal cancer, gastrointestinal stromal tumors, ovarian cancer, and several leukemias.Genomically guided therapies have produced durable responses in these diseases [7].What remains unanswered is how broadly applicable this paradigm will be to the overall population of cancer patients.To date, many large NGS efforts have resulted in disappointingly low rates of enrollment into clinical trials designed to test responses to genomically guided treatments [8,9].Careful analysis of these data suggests that this low rate reflects a clinical research system that is ill-suited to provision of rational therapeutic options for patients profiled by large-panel NGS assays rather than the absence of potentially actionable alterations detected by this technology.Major barriers to genomically matching patients include the availability of relevant trials, physician and patient knowledge of these studies, and geographical access to studies.Moreover, the diversity of tumor types that can harbor potentially targetable alterations, as well as the rarity of many of these
Source: PLoS Medicine
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,460
OpenAlex ID: W2591261220