The resistance phenotype in the development and treatment of cancer

Lancet Oncol. 2000 Dec;1:235-41. doi: 10.1016/s1470-2045(00)00154-6.


Phenotypic resistance, acquired early in carcinogenesis, has an established role in the pathogenesis of cancer in well-characterised experimental systems, and possibly also has a role in the origin of human cancer. It has been suggested that sunlight, an established risk factor for human skin carcinogenesis, is able to induce rare altered cells resistant to toxicity and to favour their clonal expansion via toxic effects exerted on normal keratinocytes. Other major risk factors for human neoplasia, including smoking and ageing, may also act partly through imposition of a constrained growth environment in the target organ to favour the emergence of altered resistant cells. Strategies aimed at counteracting this constrained environment could be effective in attenuating the force that sustains clonal expansion of altered cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Resistance / genetics*
  • Drug Resistance / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Phenotype*
  • Rats
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Treatment Failure


  • Antineoplastic Agents