Stresses in the metastatic cascade: Molecular mechanisms and therapeutic opportunities

Minhong Shen, Yibin Kang

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


Metastasis is the ultimate “survival of the fittest” test for cancer cells, as only a small fraction of disseminated tumor cells can overcome the numerous hurdles they encounter during the transition from the site of origin to a distinctly different distant organ in the face of immune and therapeutic attacks and various other stresses. During cancer progression, tumor cells develop a variety of mechanisms to cope with the stresses they encounter, and acquire the ability to form metastases. Restraining these stress-releasing pathways could serve as potentially effective strategies to prevent or reduce metastasis and improve the survival of cancer patients. Here, we provide an overview of the tumor-intrinsic, microenvironment- and treatment-induced stresses that tumor cells encounter in the metastatic cascade and the molecular pathways they develop to relieve these stresses. We also summarize the preclinical and clinical studies that evaluate the potential therapeutic benefit of targeting these stress-relieving pathways.

Original languageEnglish (US)
Pages (from-to)1577-1598
Number of pages22
JournalGenes and Development
Issue number23-24
StatePublished - Dec 1 2020

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology


  • Cancer therapeutics
  • Metastasis
  • Stress
  • Tumor microenvironment


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