Whole-genome mapping of small-molecule targets for cancer medicine

Curr Opin Chem Biol. 2020 Jun:56:42-50. doi: 10.1016/j.cbpa.2019.12.005. Epub 2020 Jan 21.

Abstract

Cancers display intratumoral and intertumoral heterogeneity, which poses challenges to small-molecule intervention. Studying drug responses on a whole-genome and transcriptome level using next-generation sequencing has revolutionized our understanding of how small molecules intervene in cells, which helps us to study and potentially predict treatment outcomes. Some small molecules act directly at the genomic level by targeting DNA or chromatin proteins. Here, we review recent advances in establishing whole-genome and transcriptome maps of small-molecule targets, comprising chromatin components or downstream events. We also describe recent advances in studying drug responses using single-cell RNA and DNA sequencing. Furthermore, we discuss how this fundamental research can be taken forward to devise innovative personalized treatment modalities.

Keywords: Cancer; Chem-seq; ChiP-seq; NGS; RNA-seq; Sequencing; Small molecule.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Chromosome Mapping / methods*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • G-Quadruplexes
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism
  • Single-Cell Analysis
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology
  • Transcriptome / genetics*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Nucleic Acids
  • Small Molecule Libraries