Combinatorial drug therapy for cancer in the post-genomic era

Nat Biotechnol. 2012 Jul 10;30(7):679-92. doi: 10.1038/nbt.2284.


Over the past decade, whole genome sequencing and other 'omics' technologies have defined pathogenic driver mutations to which tumor cells are addicted. Such addictions, synthetic lethalities and other tumor vulnerabilities have yielded novel targets for a new generation of cancer drugs to treat discrete, genetically defined patient subgroups. This personalized cancer medicine strategy could eventually replace the conventional one-size-fits-all cytotoxic chemotherapy approach. However, the extraordinary intratumor genetic heterogeneity in cancers revealed by deep sequencing explains why de novo and acquired resistance arise with molecularly targeted drugs and cytotoxic chemotherapy, limiting their utility. One solution to the enduring challenge of polygenic cancer drug resistance is rational combinatorial targeted therapy.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Drug Design*
  • Genetic Heterogeneity
  • Genome, Human
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Metabolic Networks and Pathways / genetics
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Precision Medicine