Senescence and cancer — role and therapeutic opportunities

Schmitt, Clemens A.; Wang, Boshi; Demaria, Marco

doi:10.1038/s41571-022-00668-4

Cited by 326 publications

(209 citation statements)

References 248 publications

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“…In turn, cells trigger firm proliferative arrest and senescence by initiating key cell cycle arrest genes such as TP53, p16INK4a, and p21, which counteract malignant growth. 485 In PTEN loss-induced cellular senescence, cells activate mTOR-p53-mediated signaling to block the cell cycle, and induce a cellular senescence phenotype. 486 In addition, cells undergoing senescence enhance tumor suppression by cell-extrinsic manner.…”

Section: Cancermentioning

confidence: 99%

“…Senescent cells promote senescence or death of neighboring cells through direct cell-cell interactions or inflammatory SASP factors release, causing increased production of ROS and a sustained DNA damage response, thereby also limiting the proliferation of neighboring precancerous or cancerous cells. 485 In addition, SASP factors containing immune surveillance enhancers such as CCL2, IL-15, CXCL1, etc. that drive macrophages, lymphocytes and NK cells to recruit to tumor sites, which activate immune surveillance.…”

Section: Cancermentioning

confidence: 99%

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Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

467

160

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Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

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Section: Cancermentioning

confidence: 99%

Section: Cancermentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

467

160

View full text Add to dashboard Cite

show abstract

“…However, on the other hand it has been reported that senescent cells may also promote tumor growth. Important to mention are the tumor-promoting properties of SASP including chronic inflammation, angiogenesis, stemness, migration and invasion [ 49 , 50 ]. Therefore, TIS is an important determinant of therapy response for the clinical outcome for patients and rather under-investigated.…”

Section: Therapy-induced Cellular Senescence In Pcamentioning

confidence: 99%

Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer

et al. 2022

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Background Prostate cancer (PCa) is an age-related malignancy in men with a high incidence rate. PCa treatments face many obstacles due to cancer cell resistance and many bypassing mechanisms to escape therapy. According to the intricacy of PCa, many standard therapies are being used depending on PCa stages including radical prostatectomy, radiation therapy, androgen receptor (AR) targeted therapy (androgen deprivation therapy, supraphysiological androgen, and AR antagonists) and chemotherapy. Most of the aforementioned therapies have been implicated to induce cellular senescence. Cellular senescence is defined as a stable cell cycle arrest in the G1 phase and is one of the mechanisms that prevent cancer proliferation. Results In this review, we provide and analyze different mechanisms of therapy-induced senescence (TIS) in PCa and their effects on the tumor. Interestingly, it seems that different molecular pathways are used by cancer cells for TIS. Understanding the complexity and underlying mechanisms of cellular senescence is very critical due to its role in tumorigenesis. The most prevalent analyzed pathways in PCa as TIS are the p53/p21WAF1/CIP1, the p15INK4B/p16INK4A/pRb/E2F/Cyclin D, the ROS/ERK, p27Kip1/CDK/pRb, and the p27Kip1/Skp2/C/EBP β signaling. Despite growth inhibition, senescent cells are highly metabolically active. In addition, their secretome, which is termed senescence-associated secretory phenotype (SASP), affects within the tumor microenvironment neighboring non-tumor and tumor cells and thereby may regulate the growth of tumors. Induction of cancer cell senescence is therefore a double-edged sword that can lead to reduced or enhanced tumor growth. Conclusion Thus, dependent on the type of senescence inducer and the specific senescence-induced cellular pathway, it is useful to develop pathway-specific senolytic compounds to specifically targeting senescent cells in order to evict senescent cells and thereby to reduce SASP side effects.

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“…Upon p53 activation, the up-regulation of p21 (also known as CDKN1A) blocks the formation of cyclin-cyclin-dependent kinase (CDK) complexes. p16 Ink4A (also known as CDKN2A) directly binds to and inhibits the interaction between CDK4/6 and cyclin D. When CDKs are inhibited by p21 and p16 Ink4A , RB remains hypophosphorylated and interacts with the transcription factor, E2F, leading to irreversible cell cycle arrest [ 1 , 10 ]. Although senescent cells are characterized by growth arrest, they remain metabolically active.…”

Section: Cellular Senescence: Types and Characteristicsmentioning

confidence: 99%

Mechanisms of RNA and Protein Quality Control and Their Roles in Cellular Senescence and Age-Related Diseases

Kang

Baek

Lee

2022

Cells

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Cellular senescence, a hallmark of aging, is defined as irreversible cell cycle arrest in response to various stimuli. It plays both beneficial and detrimental roles in cellular homeostasis and diseases. Quality control (QC) is important for the proper maintenance of cellular homeostasis. The QC machineries regulate the integrity of RNA and protein by repairing or degrading them, and are dysregulated during cellular senescence. QC dysfunction also contributes to multiple age-related diseases, including cancers and neurodegenerative, muscle, and cardiovascular diseases. In this review, we describe the characters of cellular senescence, discuss the major mechanisms of RNA and protein QC in cellular senescence and aging, and comprehensively describe the involvement of these QC machineries in age-related diseases. There are many open questions regarding RNA and protein QC in cellular senescence and aging. We believe that a better understanding of these topics could propel the development of new strategies for addressing age-related diseases.

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Senescence and cancer — role and therapeutic opportunities

Cited by 326 publications

References 248 publications

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer

Mechanisms of RNA and Protein Quality Control and Their Roles in Cellular Senescence and Age-Related Diseases

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