ArticleCell death and differentiation2020
BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Stress granules and RNA-binding proteins in cellular senescence: a modular perspective on stress adaptation and inflammation.Molecular biology reports · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Review
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- IAP Antagonists Selectively Eliminate Therapy-Induced Senescent Cancer Cells via TNFα-Independent Apoptosis.Cancer science · 2026Article
- Mitochondrial bioenergetics-SASP crosstalk determines senolytic efficacy in therapy-induced senescence.Cell death discovery · 2026Article
- Cancer Cell Dormancy and Chemotherapy Resistance.Journal of Cancer · 2026Review
- Therapy-induced senescence in breast cancer and cardiovascular disease: a double-edged biological process.Frontiers in cardiovascular medicine · 2026Review
- Differential responses to the combination of navitoclax and venetoclax with doxorubicin in murine models of triple negative breast cancer.Frontiers in cell and developmental biology · 2026Article
- Cellular Senescence as a Risk Factor in Head and Neck Cancer-Diagnostic and Therapeutic Perspective.Cancers · 2025Review
- Navitoclax acts synergistically with irradiation to induce apoptosis in preclinical models of H3K27M-altered diffuse midline glioma.Scientific reports · 2025Article
- TIPIN coordinates ATM-dependent checkpoint and NF-κB signaling to counteract DNA replication damage from topoisomerase inhibition.Communications biology · 2025Article
- Unleashing endogenous regeneration by senolytics.Journal of translational medicine · 2025Review
- Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax.Research square · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
TP53 wild-type breast tumors rarely undergo a complete pathological response after chemotherapy treatment. These patients have an extremely poor survival rate and studies show these tumors preferentially undergo senescence instead of apoptosis. These senescent cells persist after chemotherapy and secrete cytokines and chemokines comprising the senescence associated secretory phenotype, which promotes survival, proliferation, and metastasis. We hypothesized that eliminating senescent tumor cells would improve chemotherapy response and extend survival. Previous studies have shown "senolytic" agents selectively kill senescent normal cells, but their efficacy in killing chemotherapy-induced senescent cancer cells is unknown. We show that ABT-263, a BH3 mimetic that targets antiapoptotic proteins BCL2/BCL-XL/BCL-W, had no effect on proliferating cells, but rapidly and selectively induced apoptosis in a subset of chemotherapy-treated cancer cells, though sensitivity required days to develop. Low NOXA expression conferred resistance to ABT-263 in some cells, necessitating additional MCL1 inhibition. Gene editing confirmed breast cancer cells relied on BCL-XL or BCL-XL/MCL1 for survival in senescence. In a mouse model of breast cancer, ABT-263 treatment following chemotherapy led to apoptosis, greater tumor regression, and longer survival. Our results reveal cancer cells that have survived chemotherapy by entering senescence can be eliminated using BH3 mimetic drugs that target BCL-XL or BCL-XL/MCL1. These drugs could help minimize residual disease and extend survival in breast cancer patients that otherwise have a poor prognosis and are most in need of improved therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.