title: Evolving landscape of tumor molecular profiling for personalized cancer therapy: a comprehensive review.
abstract: BACKGROUND
  Tumour molecular profiling has been at the crossroads of large-scale integrative genomic studies and major clinical trials over the past 5 years and has provided roadmaps for better disease stratification and therapeutic management.
  
  
  METHODS
  We review the landscape of precision oncology trials in Asia, Europe and the United States, and emerging insights gained from recently reported studies such as the SHIVA and CUSTOM trials. Changes in the molecular portraits of human cancers and the immune contexture of the tumor microenvironment during treatment may predict the course of tumor progression, including the development of treatment resistance. 'Liquid biopsy' approaches that harness circulating tumor cells, cell-free DNA and exosomes may provide a non-invasive means of monitoring the parent tumor in real-time. Several molecular signatures are being evaluated as biomarkers for emerging immunologic approaches, such as the mismatch-repair deficiency status and nonsynonymous mutation burden in anti-PD-1 immune checkpoint blockade. Finally, we review the current actionability and future clinical impact of multigene panel and next-generation sequencing (NGS)-based profiling.
  
  
  CONCLUSIONS
  In the future, molecular profiling may help to fulfill unmet needs for predictive biomarkers in novel immunotherapeutic approaches, while ongoing precision trials are laying the foundations for clinical uptake of NGS testing.
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Nicholas Li-Xun
authors.initials: NL
authors.lastname: Syn
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Yong
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute, National University Health System , Singapore , Singapore.
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor
keywords: Whole-genome sequencing; cancer genomics; cancer immunology; exosomes; immunotherapy; liquid biopsy; next-generation sequencing; precision oncology; tumour microenvironment; whole-exome sequencing