title: The possibility of clinical sequencing in the management of cancer.
abstract: Comprehensive genomic profiling using next-generation sequencing technologies provides insights into understanding the genomic architecture of human cancer. This new understanding of the cancer genome allows us to identify many more genomic alterations occurring within tumors than before, some of which could be potential therapeutic targets through molecular targeted agents. Currently, a large number of molecular targeted agents are being developed, and consequently, cancer treatment is rapidly shifting from empiric therapy employing cytotoxic anticancer drugs to genotype-directed therapy using molecular targeted agents. In current daily clinical practice, hotspot-based single-gene assays that detect RAS mutations in colorectal cancer or EGFR mutations in non-small cell lung cancer are widely used to identify variants. However, it is becoming evident that more comprehensive genomic analysis is crucial in identifying the patient population that may benefit from molecular targeted therapy and the accelerated development of novel drugs for early clinical trials. For these purposes, an increasing number of gene panel-based targeted sequencing is commercially available in clinical practice from sequencing companies. Despite several challenges in implementing this approach, comprehensive genomic profiling and identification of actionable mutations is likely to become one of the standard options in the management of cancer in the near future. The use of clinical sequencing has the potential to usher a new era in precision medicine for cancer diagnosis and treatment. In this review, we discuss the application of comprehensive genomic profiling using next-generation sequencing technologies in clinical oncology and address the current challenges for its implementation.
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kou
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanai
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto mmuto@kuhp.kyoto-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Muto
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: actionable mutation; gene panel; molecular targeted therapy; next-generation sequencing; precision medicine