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Combinatorial drug therapy for cancer in the post-genomic era

Bissan Al-Lazikani1, Udai Banerji, Paul Workman

  • 1Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, UK. bissan.al-lazikani@icr.ac.uk

Nature Biotechnology
|July 12, 2012
PubMed

Insights

Personalized cancer medicine uses

Area of Science:

  • 'Omics' technologies and cancer genomics
  • Translational oncology and drug discovery
  • Tumorigenesis and cancer genetics

Background:

  • Whole genome sequencing and 'omics' technologies identify tumor vulnerabilities.
  • Cancer cells exhibit dependencies on specific mutations, termed 'addictions'.
  • These vulnerabilities offer targets for precision cancer therapies.

Purpose of the Study:

  • To discuss the shift from conventional chemotherapy to personalized cancer medicine.
  • To address the challenge of drug resistance driven by intratumor heterogeneity.
  • To propose combinatorial targeted therapy as a solution for polygenic resistance.

Main Methods:

  • Review of advances in whole genome sequencing and 'omics' technologies.
  • Analysis of genetic heterogeneity in tumors.
  • Conceptual framework for rational combinatorial targeted therapy.

Main Results:

  • Personalized medicine targets genetically defined patient subgroups.
  • Intratumor genetic heterogeneity drives resistance to targeted and cytotoxic drugs.
  • Combinatorial targeted therapy is a promising strategy to overcome polygenic resistance.

Conclusions:

  • Personalized cancer medicine offers an alternative to traditional chemotherapy.
  • Overcoming drug resistance requires addressing tumor heterogeneity.
  • Rational combinatorial targeted therapy is essential for durable cancer treatment.

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