Lack of predictive tools for conventional and targeted cancer therapy: Barriers to biomarker development and clinical translation

Adv Drug Deliv Rev. 2021 Sep:176:113854. doi: 10.1016/j.addr.2021.113854. Epub 2021 Jun 27.

Abstract

Predictive tools, utilising biomarkers, aim to objectively assessthe potentialresponse toa particular clinical intervention in order to direct treatment.Conventional cancer therapy remains poorly served by predictive biomarkers, despite being the mainstay of treatment for most patients. In contrast, targeted therapy benefits from a clearly defined protein target for potential biomarker assessment. We discuss potential data sources of predictive biomarkers for conventional and targeted therapy, including patient clinical data andmulti-omicbiomarkers (genomic, transcriptomic and protein expression).Key examples, either clinically adopted or demonstrating promise for clinical translation, are highlighted. Following this, we provide an outline of potential barriers to predictive biomarker development; broadly discussing themes of approaches to translational research and study/trial design, and the impact of cellular and molecular tumor heterogeneity. Future avenues of research are also highlighted.

Keywords: Intra-tumoral heterogeneity; Liquid biopsy; Multi-omics; Predictive biomarker; Predictive signature; Predictive tool; Treatment response; Trial design; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Gene Expression Profiling
  • Genomics / methods
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Proteins / metabolism
  • Translational Research, Biomedical / methods

Substances

  • Biomarkers, Tumor
  • Proteins