Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges.
Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges.
J Clin Oncol. 2013 Apr 15;
Dienstmann R, Rodon J, Barretina J, Tabernero J
Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biologic sense of the substantial genomic data derived from multiple platforms. We define two different approaches for the analysis, interpretation, and clinical applicability of genomic data: (1) the genomically stratified model originates from the “one test-one drug” paradigm and is currently being expanded with an upfront multicategorical approach following recent advances in multiplexed genotyping platforms; and (2) the comprehensive assessment model is based on whole-genome, -exome, and -transcriptome data and allows identification of novel drivers and subsequent therapies in the experimental setting. Tumor heterogeneity and evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will need to be addressed in the new scenario of early drug development. Logistical issues related to prescreening strategies and trial allocation, in addition to concerns in the economic and ethical domains, must be taken into consideration. Here we present a historical view of how increased understanding of cancer genomics has been translated to the clinic and discuss the prospects and challenges for further implementation of a personalized treatment strategy for human solid tumors. HubMed – drug
Building a Personalized Medicine Infrastructure at a Major Cancer Center.
J Clin Oncol. 2013 Apr 15;
Meric-Bernstam F, Farhangfar C, Mendelsohn J, Mills GB
Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual’s own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have entered clinical trials creating a huge opportunity to couple genomic markers with this emerging drug tool kit. The number of patients managed in major cancer centers creates a challenge to the implementation of genomic technologies required to successfully deliver on the promise of personalized cancer care. This requires a major investment in infrastructure to facilitate rapid deployment of multiplex, cost-effective, and tissue-sparing assays relevant across multiple tumor lineages in the Clinical Laboratory Improvement Amendments (CLIA) environment. Efforts must be made to ensure that assays are accessible to patients most likely to be enrolled onto molecular-marker-driven trials and that the tests are billable and payable, which will make them accessible to a wide range of patients. As the number of patients and aberrations increase, it will become critical to provide decision support for genomic medicine. Institutional commitment is needed to optimize accessibility and quality of research biopsies and to facilitate novel personalized cancer therapy trials. This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy. HubMed – drug