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Detecting markers of therapy-induced senescence in cancer cells

Item Type:Article
Title:Detecting markers of therapy-induced senescence in cancer cells
Creators Name:Fan, D.N.Y. and Schmitt, C.A.
Abstract:Therapy-induced senescence (TIS), a lasting chemotherapy-evoked proliferative arrest of tumor cells, has gained increasing attention by cancer researchers because of its' profound biological implications, and by clinical oncologists due to its potential contribution to the long-term outcome of cancer patients post-treatment. Although both apoptosis and senescence represent therapy-inducible, ultimate cell-cycle exit programs, mediated via DNA damage response signaling, apoptotic cell death as the faster and often quantitatively more prominent tumor response has been in the scientific focus for decades. The more recently recognized TIS as another "safeguard" response of cancer cells that were never primed for or failed to execute apoptosis, not only reflects a more complex "arrest-plus-other features" cell-autonomous condition but produces non-cell-autonomous phenotypes at the tumor site, collectively impinging on tumor control and clinical outcome. Hence, TIS research is gaining pivotal interest from both a tumor biological and a therapeutic perspective, and the development of non-DNA damaging, senescence-evoking therapeutics is about to become a major research objective. In this chapter, we describe a well-characterized, genetically controlled TIS model system based on primary BCL2-expressing Emu-myc transgenic lymphoma cells harboring defined genetic lesions and provide protocols for co-staining of either senescence-associated beta-galactosidase (SA-beta-gal) activity or trimethylated lysine 9 of histone H3 (H3K9me3) together with Ki67 to detect the senescent status of therapy-exposed cancer cells.
Keywords:Cancer, Chemotherapy, DNA Damage Response, Heterochromatin, H3K9me3, Ki67, SA-beta-gal, Senescence-Associated beta-Galactosidase, Senescence Markers, Therapy-Induced Senescence (TIS), TIS Model System
Source:Methods in Molecular Biology
Series Name:Methods in Molecular Biology
Title of Book:Oncogene-induced senescence : methods and protocols
Publisher:Springer / Humana Press
Page Range:41-52
Official Publication:https://doi.org/10.1007/978-1-4939-6670-7_4
PubMed:View item in PubMed

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