Hallmarks of senescence in carcinogenesis and cancer therapy

Jerry W. Shay, Igor B. Roninson

Research output: Contribution to journalArticle

394 Citations (Scopus)

Abstract

Cellular senescence is a signal transduction program leading to irreversible cell cycle arrest. This growth arrest can be triggered by many different mechanisms including recognition by cellular sensors of DNA double-strand breaks leading to the activation of cell cycle checkpoint responses and recruitment of DNA repair foci. Senescence is initiated by the shortening of telomeres (replicative senescence) or by other endogenous and exogenous acute and chronic stress signals (STASIS: stress or aberrant signaling-induced senescence). The process of carcinogenesis involves a series of changes that allow tumor cells to bypass the senescence program. Nevertheless, tumor cells retain the capacity to undergo senescence. Treatment of tumor cells with many conventional anticancer therapies activates DNA damage signaling pathways, which induce apoptosis in some cells and senescence in others. Overexpression of tumor suppressors or inhibition of oncogenes can also induce rapid senescence in tumor cells. Senescent cells, while not dividing, remain metabolically active and produce many secreted factors, some of which stimulate and others inhibit the growth of tumors. The emerging knowledge about the pathways that lead to senescence and determine the pattern of gene expression in senescent cells may lead to more effective treatments for cancer.

Original languageEnglish (US)
Pages (from-to)2919-2933
Number of pages15
JournalOncogene
Volume23
Issue number16 REV. ISS. 2
DOIs
StatePublished - Apr 12 2004

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Carcinogenesis
Cell Aging
Neoplasms
Cell Cycle Checkpoints
Therapeutics
Telomere Shortening
Double-Stranded DNA Breaks
Growth
Oncogenes
DNA Repair
DNA Damage
Signal Transduction
Apoptosis
Gene Expression

Keywords

  • Apoptosis
  • Chemotherapy
  • Mitotic catastrophe
  • Replicative senescence
  • STASIS
  • Telomeres

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Hallmarks of senescence in carcinogenesis and cancer therapy. / Shay, Jerry W.; Roninson, Igor B.

In: Oncogene, Vol. 23, No. 16 REV. ISS. 2, 12.04.2004, p. 2919-2933.

Research output: Contribution to journalArticle

Shay, Jerry W. ; Roninson, Igor B. / Hallmarks of senescence in carcinogenesis and cancer therapy. In: Oncogene. 2004 ; Vol. 23, No. 16 REV. ISS. 2. pp. 2919-2933.
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