Evolving landscape of tumor molecular profiling for personalized cancer therapy: a comprehensive review

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Whole-genome sequencing
• precision oncology
• cancer genomics
• immunotherapy
• next-generation sequencing
• liquid biopsy
• tumour microenvironment
• cancer immunology
• exosomes
• whole-exome sequencing

Article highlights

• Comprehensive tumour molecular characterisation has provided unprecedented insights into cancer biology

• Molecular prescreening is increasingly being planned into transformative clinical trials of targeted therapies and immunotherapies

• Molecular profiling is currently being harnessed in a number of settings, such as in the diagnostic work-up of unknown primary carcinomas, drug developmental programmes, and studies elucidating the effect of spatiotemporal heterogeneity and tumour microenvironment on cancer therapy

• It is likely that tumour molecular profiling will advance ‘liquid biopsy’ approaches and ‘precision immunotherapy’ in the future

• Several challenges remain before comprehensive molecular profiling may be implemented on a large-scale

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.