# Cellular senescence

Source: https://onco.cc/pathways/senescence/  
OnCo record `senescence` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Damaged cells can stop dividing permanently instead of dying. That protects against cancer at first, but senescent cells linger, secrete inflammatory signals, and after chemotherapy can help tumours relapse, so removing them (senolytics) is a new strategy.

## Summary

Oncogene-induced and therapy-induced senescence engage p53/p21 and p16/RB to arrest the cycle; the senescence-associated secretory phenotype (SASP: IL-6, IL-8, MMPs) remodels the microenvironment, promotes inflammation, immune recruitment, and paradoxically tumour progression and treatment resistance. 'One-two punch' therapy induces senescence (e.g., CDK4/6 inhibitors, chemotherapy) then clears it with senolytics (BCL-XL/BCL-2 inhibitors, navitoclax; dasatinib+quercetin; uPAR CAR-T in mice). Senescent cells are a 2022 hallmark. Clinical proof in oncology is early; toxicity of BCL-XL inhibition (platelets) drives PROTAC approaches.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: Retired workers who refuse to leave the office. They no longer do the job, but they shout, clutter the corridors, and sometimes hire back the very people who were fired.
- Interventions: Senescence-inducing therapy (CDK4/6 inhibitors, chemotherapy, radiation) followed by senolytics (one-two punch); Navitoclax and BCL-XL PROTACs; uPAR-targeted CAR-T (preclinical); SASP modulation with JAK inhibitors or IL-6 blockade

## Notes

- Leading programmes: Lowe (MSK) on senescence and immune clearance; Campisi legacy (Buck); Kirkland (Mayo) on senolytics; Demaria (ERIBA Groningen); Peeper (NKI) on one-two punch.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cellular_senescence
- Schmitt, Wang & Demaria, Senescence and cancer: role and therapeutic opportunities (Nature Reviews Clinical Oncology 2022): https://doi.org/10.1038/s41571-022-00668-4

## Connected records

- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/), [Epigenetic age after cancer treatment](https://onco.cc/technologies/rejuv-age-epigenetic-clocks/), [Senescent cells and p16 after chemotherapy](https://onco.cc/technologies/rejuv-age-senescent-cells-after-treatment/), [Senolytics after cancer treatment](https://onco.cc/technologies/rejuv-frontier-senolytics/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [CDK4/6](https://onco.cc/targets/cdk4-6/), [CDKN1A](https://onco.cc/targets/cdkn1a/), [CDKN2A](https://onco.cc/targets/cdkn2a/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Mayo Clinic](https://onco.cc/institutions/mayo-clinic/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [Telomere maintenance & replicative immortality](https://onco.cc/pathways/telomere-maintenance/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Ageing tissue and clonal fields: cancer as a disease of old tissue](https://onco.cc/terms/ageing-tissue-field-theory/), [Hallmark (2022): senescent cells](https://onco.cc/terms/senescent-cells/), [Hallmark: enabling replicative immortality](https://onco.cc/terms/enabling-replicative-immortality/)
- key papers: [Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells](https://onco.cc/key-papers/paper-hallmarks-new-dimensions-cancer-discov-2022/), [Senescence and cancer - role and therapeutic opportunities](https://onco.cc/key-papers/paper-schmitt-nat-rev-clin-oncol/)
- ideas: [One-two punch: clear senescent cells after chemotherapy](https://onco.cc/ideas/idea-senolytics-after-chemo/)

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JSON: https://onco.cc/api/v1/entities/senescence.json