Chemotherapy-Induced Metastasis: Molecular Mechanisms, Clinical Manifestations, Therapeutic Interventions

Cancer Res. 2019 Sep 15;79(18):4567-4576. doi: 10.1158/0008-5472.CAN-19-1147. Epub 2019 Aug 20.


Chemotherapy offers long-term clinical benefits to many patients with advanced cancer. However, recent evidence has linked the cytotoxic effects of chemotherapy with the de novo elicitation of a prometastatic tumor microenvironment. This "modified" tumor microenvironment is triggered by a chemotherapy-driven cytokine storm or through direct effects of certain chemotherapeutics on stromal and/or immune cells, the most critical being tumor-associated macrophages. These chemotherapy-educated cells act as facilitators in tumor-host cell interactions promoting the establishment of distant metastasis. Certain clinical studies now offer substantial evidence that prometastatic changes are indeed identified in the tumor microenvironment of certain patient subpopulations, especially those that do not present with any pathologic response after neoadjuvant chemotherapy. Deciphering the exact contextual prerequisites for chemotherapy-driven metastasis will be paramount for designing novel mechanism-based treatments for circumventing chemotherapy-induced metastasis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Cell Movement
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Neoadjuvant Therapy / adverse effects*
  • Neoplasm Metastasis
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*


  • Antineoplastic Agents