Stresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities.

TitleStresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities.
Publication TypeJournal Article
Year of Publication2020
AuthorsShen, M, Kang, Y
JournalGenes Dev
Volume34
Issue23-24
Pagination1577-1598
Date Published2020 12 01
ISSN1549-5477
KeywordsAntineoplastic Agents, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Metastasis, Neoplasms, Stress, Physiological, Tumor Microenvironment
Abstract

<p>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.</p>

DOI10.1101/gad.343251.120
Alternate JournalGenes Dev
PubMed ID33262145
PubMed Central IDPMC7706714