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Review
. 2021 Feb 4;13(4):612.
doi: 10.3390/cancers13040612.

Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies

Philipp Ernst  1   2 , Florian H Heidel  3   4
Affiliations
Review

Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies

Philipp Ernst et al. Cancers (Basel). .

Abstract

Senescence is a cellular state that is involved in aging-associated diseases but may also prohibit the development of pre-cancerous lesions and tumor growth. Senescent cells are actively secreting chemo- and cytokines, and this senescence-associated secretory phenotype (SASP) can contribute to both early anti-tumorigenic and long-term pro-tumorigenic effects. Recently, complex mechanisms of cellular senescence and their influence on cellular processes have been defined in more detail and, therefore, facilitate translational development of targeted therapies. In this review, we aim to discuss major molecular pathways involved in cellular senescence and potential therapeutic strategies, with a specific focus on myeloid malignancies.

Keywords: SASP; leukemia; myelodysplastic syndrome; myeloproliferative neoplasms; senescence; senolytics.

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Conflict of interest statement

Florian H. Heidel received fees for consulting services and research funding from Novartis, Celgene, and Philipp Ernst declares no conflict of interest.

Figures

Figure 1
Figure 1
Pathways in cellular senescence. Schematic representation of the major pathways of cellular senescence and selected compounds for senescence induction or senolysis. HMT, Histone methyltransferase. Other abbreviations are explained in the text in detail.
Figure 2
Figure 2
Pathways responsible for the induction of the senescence-associated secretory phenotype (SASP). Schematic representation of major pathways that are activated in senescent cells leading to the expression of SASP genes (left panel). Most important SASP factors according to [68,69,70] (right panel). cDN, cyclic dinucleotides. ECM, Extracellular matrix. ub, Ubiquitin.
See this image and copyright information in PMC

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