title: Application of molecular profiling in clinical trials for advanced metastatic cancers.
abstract: There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach.
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL). kummars@mail.nih.gov.
authors: Shivaani
authors: S
authors: Kummar
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: P Mickey
authors: PM
authors: Williams
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Chih-Jian
authors: CJ
authors: Lih
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Eric C
authors: EC
authors: Polley
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Alice P
authors: AP
authors: Chen
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Larry V
authors: LV
authors: Rubinstein
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Yingdong
authors: Y
authors: Zhao
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Richard M
authors: RM
authors: Simon
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: Barbara A
authors: BA
authors: Conley
authors: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (SK, ECP, APC, LVR, YZ, RMS, BAC, JHD); Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (PMW, CJL).
authors: James H
authors: JH
authors: Doroshow
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor