The pan-therapeutic resistance of disseminated tumor cells: Role of phenotypic plasticity and the metastatic microenvironment

Semin Cancer Biol. 2020 Feb;60:138-147. doi: 10.1016/j.semcancer.2019.07.021. Epub 2019 Jul 31.


Cancer metastasis is the leading cause of mortality in patients with solid tumors. The majority of these deaths are associated with metastatic disease that occurs after a period of clinical remission, anywhere from months to decades following removal of the primary mass. This dormancy is prominent in cancers of the breast and prostate among others, leaving the survivors uncertain about their longer-term prognosis. The most daunting aspect of this dormancy and re-emergence is that the micrometastases in particular, and even large lethal outgrowths are often show resistance to agents to which they have not been exposed. This suggests that in addition to specific mutations that target single agents, there also exist adaptive mechanisms that provide this pan-resistance. Potential molecular underpinnings of which are the topic of this review.

Keywords: Disseminated tumor cells; Dormancy; Epithelial-mesenchymal plasticity; Metastasis; Metastatic microenvironment; Therapeutic resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Plasticity
  • Disease Progression
  • Drug Resistance, Neoplasm* / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Immunomodulation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms / drug therapy*
  • Neoplasms / etiology
  • Neoplasms / pathology*
  • Tumor Escape
  • Tumor Microenvironment* / genetics