{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:59:43Z","timestamp":1791237583475,"version":"4.1.0"},"reference-count":95,"publisher":"Radiation Research Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:p>Radiation-induced senescence (RIS) is thought to be one mechanism by which tumor cells can survive radiation-induced cell death. Accumulating evidence suggests that therapy-induced senescence (TIS) (triggered by both chemotherapy and\/or irradiation) also facilitates tumor cell recovery, thereby contributing to disease recurrence. Furthermore, the factors secreted by senescent tumor cells (the senescence-associated secretory phenotype (SASP)) have, in some cases, been reported to be tumor-promoting, immunosuppressive, and potentially responsible for some of the adverse effects of radiation. Given these largely undesirable attributes of RIS in tumor cells, the use of senolytic agents to eliminate senescent tumor cells has been investigated in preclinical studies. An analysis of the available literature on RIS in cell culture models tends to support the utility of the Bcl-xL\/Bcl-2\/Bcl-wtargeting agent ABT-263 (navitoclax), in combination with a single high-dose of radiation and, in some cases, with fractionated irradiation. However, because drug action has also been reported when administered prior to irradiation, prior tumor cell entry into senescence may not be obligatory for enhancement of radiation sensitivity by ABT-263. This conclusion is also consistent with drug action against tumor cells with low RIS levels, such as those induced by fractionated irradiation. While a relatively small number of studies in tumor-bearing animals demonstrate the effectiveness of ABT-263 in combination with radiation in vivo, once the drug pressure has been relaxed, the tumor cells likely still retain the capacity to recover proliferative capacity. Since ABT-263 is unlikely to be approved for the clinical treatment of solid tumors due to both on-target (thrombocytopenia) and off-target (neutropenia) toxicities, the few studies indicating improved radiosensitivity with ABT-199 (venetoclax) are intriguing, suggesting that targeting of Bcl-xL may not be a strict requirement for the combination strategy. Finally, it is worth noting that senolytic agents have the potential to protect normal tissue from radiation-induced damage, which may prove to be the most clinically relevant observation for this class of drugs.<\/jats:p>","DOI":"10.1667\/rade-25-00156.1","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:10:02Z","timestamp":1770837002000},"page":"484-501","source":"Crossref","is-referenced-by-count":1,"title":["Assessing the Complexities of Utilizing BH3 Mimetics for a Senolytic Strategy in Combination with Ionizing Radiation"],"prefix":"10.1667","volume":"205","author":[{"given":"Muruj","family":"Alshehri","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareq","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, Arabian Gulf University, Manama, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell S.","family":"Anscher","sequence":"additional","affiliation":[{"name":"Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan","family":"Boyd","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Harada","sequence":"additional","affiliation":[{"name":"Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Gewirtz","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"4","doi-asserted-by":"publisher","unstructured":"WL Santivasi  and F Xia  \"Antioxid Redox Signal.\"  21, \"Ionizing radiation-induced DNA damage, response, and repair.\" 251 (2014)","DOI":"10.1089\/ars.2013.5668"},{"key":"39","doi-asserted-by":"crossref","unstructured":"Y Jiao, F Cao, H Liu,  \"Health Phys.\"  123, \"Radiation-induced cell death and its mechanisms.\" 376 (2022)","DOI":"10.1097\/HP.0000000000001601"},{"key":"43","doi-asserted-by":"crossref","unstructured":"X Lang, MD Green, W Wang, et al.  \"Cancer Discov.\"  9, \"Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11.\" 1673 (2019)","DOI":"10.1158\/2159-8290.CD-19-0338"},{"key":"41","doi-asserted-by":"crossref","unstructured":"S Adjemian, T Oltean, S Martens, et al.  \"Cell Death Dis.\"  11, \"Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death.\" 1003 (2020)","DOI":"10.1038\/s41419-020-03209-y"},{"key":"2","doi-asserted-by":"crossref","unstructured":"JE Leeman, Jin-gao Li, X Pei, et al.  \"JAMA Oncol.\"  3, \"Patterns of treatment failure and postrecurrence outcomes among patients with locally advanced head and neck squamous cell carcinoma after chemoradiotherapy using modern radiation techniques.\" 1487 (2017)","DOI":"10.1001\/jamaoncol.2017.0973"},{"key":"5","doi-asserted-by":"crossref","unstructured":"T Saleh, S Bloukh, VJ Carpenter, et al.  \"Cancers.\"  12, \"Therapy-induced senescence: an \u201cold\u201d friend becomes the enemy.\" 822 (2020)","DOI":"10.3390\/cancers12040822"},{"key":"7","doi-asserted-by":"crossref","unstructured":"VJ DeLuca  and T Saleh  \"Cancer Metastasis Rev.\"  42, \"Insights into the role of senescence in tumor dormancy: mechanisms and applications.\" 19 (2023)","DOI":"10.1007\/s10555-023-10082-6"},{"key":"10","doi-asserted-by":"crossref","unstructured":"NE Sharpless  and CJ Sherr  \"Nat Rev Cancer.\"  15, \"Forging a signature of in vivo senescence.\" 397 (2015)","DOI":"10.1038\/nrc3960"},{"key":"12","doi-asserted-by":"crossref","unstructured":"MY Terzi, M Izmirli, B Gogebakan,  \"Mol Biol Rep.\"  43, \"The cell fate: senescence or quiescence.\" 1213 (2016)","DOI":"10.1007\/s11033-016-4065-0"},{"key":"13","doi-asserted-by":"crossref","unstructured":"A Hernandez-Segura, TV de Jong, S Melov, et al.  \"Curr Biol CB.\"  27, \"Unmasking transcriptional heterogeneity in senescent cells.\" 2652 (2017)","DOI":"10.1016\/j.cub.2017.07.033"},{"key":"14","doi-asserted-by":"crossref","unstructured":"M Milanovic, DNY Fan, D Belenki, et al.  \"Nature.\"  553, \"Senescence-associated reprogramming promotes cancer stemness.\" 96 (2018)","DOI":"10.1038\/nature25167"},{"key":"15","doi-asserted-by":"crossref","unstructured":"C Duy, M Li, M Teater, et al.  \"Cancer Discov.\"  11, \"Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence.\" 1542 (2021)","DOI":"10.1158\/2159-8290.CD-20-1375"},{"key":"16","doi-asserted-by":"crossref","unstructured":"T. Saleh,  \"Cell Cycle.\"  23, \"Therapy-induced senescence is finally escapable, what is next?\" 713 (2024)","DOI":"10.1080\/15384101.2024.2364579"},{"key":"17","doi-asserted-by":"crossref","unstructured":"SP Wyles, T Tchkonia, JL Kirkland,  \"Plast Reconstr Surg.\"  150, \"Targeting cellular senescence for age-related diseases: Path to clinical translation.\" 20S (2022)","DOI":"10.1097\/PRS.0000000000009669"},{"key":"18","doi-asserted-by":"crossref","unstructured":"T Saleh, EF Greenberg, AC Faber, et al.  \"Cancer Res.\"  85, \"A critical appraisal of the utility of targeting therapy-induced senescence for cancer treatment.\" 1755 (2025)","DOI":"10.1158\/0008-5472.CAN-24-2219"},{"key":"19","doi-asserted-by":"crossref","unstructured":"L Bousset  and J Gil  \"Mol Oncol.\"  16, \"Targeting senescence as an anticancer therapy.\" 3855 (2022)","DOI":"10.1002\/1878-0261.13312"},{"key":"20","doi-asserted-by":"crossref","unstructured":"I Meattini, C Becherini, L Boersma, et al.  \"Lancet Oncol.\"  23, \"European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.\" e21 (2022)","DOI":"10.1016\/S1470-2045(21)00539-8"},{"key":"21","doi-asserted-by":"crossref","unstructured":"BE Hickey, ML James, T Daly, et al.  \"Cochrane Database Syst Rev.\"  2019, \"Hypofractionation for clinically localized prostate cancer.\" CD011462 (2019)","DOI":"10.1002\/14651858.CD011462.pub2"},{"key":"22","doi-asserted-by":"crossref","unstructured":"RD Timmerman, R Paulus, HI Pass, et al.  \"JAMA Oncol.\"  4, \"Stereotactic body radiation therapy for operable early-stage lung cancer.\" 1263 (2018)","DOI":"10.1001\/jamaoncol.2018.1251"},{"key":"23","doi-asserted-by":"crossref","unstructured":"M Mayinger, R Kotecha, A Sahgal, et al.  \"Lung Cancer Amst Neth.\"  182, \"Stereotactic body radiotherapy for lung oligo-metastases: Systematic review and International Stereotactic Radiosurgery Society practice guidelines.\" 107284 (2023)","DOI":"10.1016\/j.lungcan.2023.107284"},{"key":"24","doi-asserted-by":"crossref","unstructured":"S Siva, AV Louie, R Kotecha, et al.  \"Lancet Oncol.\"  25, \"Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).\" e18 (2024)","DOI":"10.1016\/S1470-2045(23)00513-2"},{"key":"25","doi-asserted-by":"crossref","unstructured":"SH Bae, SJ Chun, JH Chung, et al.  \"Int J Radiat Oncol Biol Phys.\"  118, \"Stereotactic body radiation therapy for hepatocellular carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.\" 337 (2024)","DOI":"10.1016\/j.ijrobp.2023.08.015"},{"key":"26","doi-asserted-by":"crossref","unstructured":"N van As, C Griffin, A Tree, et al.  \"N Engl J Med.\"  391, \"Phase 3 trial of stereotactic body radiotherapy in localized prostate cancer.\" 1413 (2024)","DOI":"10.1056\/NEJMoa2403365"},{"key":"27","doi-asserted-by":"crossref","unstructured":"E Doyle, AJ Killean, S Harrow, et al.  \"Radiother Oncol J Eur Soc Ther Radiol Oncol.\"  196, \"Systematic review of the efficacy of stereotactic ablative radiotherapy for oligoprogressive disease in metastatic cancer.\" 110288 (2024)","DOI":"10.1016\/j.radonc.2024.110288"},{"key":"28","doi-asserted-by":"crossref","unstructured":"MA Vogelbaum, PD Brown, H Messersmith, et al.  \"J Clin Oncol.\"  40, \"Treatment for brain metastases: ASCO-SNO-ASTRO Guideline.\" 492 (2022)","DOI":"10.1200\/JCO.21.02314"},{"key":"29","doi-asserted-by":"crossref","unstructured":"CB Saw, S Bao, S Li,  \"J Radiat Oncol.\"  1, \"A review on the technical and dosimetric aspects of stereotactic body radiation therapy (SBRT).\" 317 (2012)","DOI":"10.1007\/s13566-012-0025-z"},{"key":"30","doi-asserted-by":"crossref","unstructured":"JA Vargo  and DE Heron  \"Front Oncol.\"  5, \"Editorial: Clinical application of stereotactic body radiotherapy (SBRT): Cranium to prostate.\" 266 (2015)","DOI":"10.3389\/fonc.2015.00266"},{"key":"31","doi-asserted-by":"crossref","unstructured":"R Pandey,  Gurumurthy, J Galinski, et al.  \"Nucl Med Radiat Ther.\"  6, \"Stereotactic body radiation therapy: A review of applications and outcomes.\" 1 (2015)","DOI":"10.4172\/2155-9619.1000229"},{"key":"33","doi-asserted-by":"crossref","unstructured":"PGS Prasanna, MM Ahmed, JA Hong, et al.  \"Lancet Oncol.\"  25, \"Best practices and novel approaches for the preclinical development of drug\u2013radiotherapy combinations for cancer treatment.\" e501 (2024)","DOI":"10.1016\/S1470-2045(24)00199-2"},{"key":"34","doi-asserted-by":"crossref","unstructured":"RA Chandra, FK Keane, FEM Voncken, et al.  \"The Lancet.\"  398, \"Contemporary radiotherapy: present and future.\" 171 (2021)","DOI":"10.1016\/S0140-6736(21)00233-6"},{"key":"35","doi-asserted-by":"publisher","unstructured":"A Begg, F Stewart, C Vens,  \"Nat Rev Cancer.\"  11, \"Strategies to improve radiotherapy with targeted drugs.\" 239 (2011)","DOI":"10.1038\/nrc3007"},{"key":"36","doi-asserted-by":"crossref","unstructured":"JA Nickoloff, L Taylor, N Sharma, et al.  \"Cancer Drug Resist.\"  4, \"Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy.\" 244 (2021)","DOI":"10.20517\/cdr.2020.89"},{"key":"38","doi-asserted-by":"crossref","unstructured":"R Huang  and PK Zhou  \"Signal Transduct Target Ther.\"  6, \"DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.\" 254 (2021)","DOI":"10.1038\/s41392-021-00648-7"},{"key":"44","doi-asserted-by":"crossref","unstructured":"BC Kim, HJ Yoo, HC Lee, et al.  \"Oncol Rep.\"  31, \"Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation.\" 2229 (2014)","DOI":"10.3892\/or.2014.3069"},{"key":"45","doi-asserted-by":"crossref","unstructured":"JM Lee, HS Kim, A Kim, et al.  \"Yonsei Med J.\"  63, \"ABT-737, a BH3 mimetic, enhances the therapeutic effects of ionizing radiation in K-ras mutant non-small cell lung cancer preclinical model.\" 16 (2022)","DOI":"10.3349\/ymj.2022.63.1.16"},{"key":"46","doi-asserted-by":"crossref","unstructured":"F Jochems, C Baltira, JA MacDonald, et al.  \"Cell Death Differ.\"  32, \"Senolysis by ABT-263 is associated with inherent apoptotic dependence of cancer cells derived from the non-senescent state.\" 855 (2025)","DOI":"10.1038\/s41418-024-01439-7"},{"key":"47","doi-asserted-by":"crossref","unstructured":"H Wu, DS Schiff, Y Lin, et al.  \"Radiat Res.\"  182, \"Ionizing radiation sensitizes breast cancer cells to Bcl-2 inhibitor, ABT-737, through regulating Mcl-1.\" 618 (2014)","DOI":"10.1667\/RR13856.1"},{"key":"48","unstructured":"PG Prasanna, DE Citrin, J Hildesheim, et al.  \"JNCI J Natl Cancer Inst.\"  113, \"Therapy-induced senescence: Opportunities to improve anticancer therapy.\" 1285 (2021)"},{"key":"51","unstructured":"PG Prasanna, DE Citrin, J Hildesheim, et al.  \"JNCI J Natl Cancer Inst.\"  113, \"Therapy-induced senescence: Opportunities to improve anticancer therapy.\" 1285 (2021)"},{"key":"49","doi-asserted-by":"crossref","unstructured":"KE Tagscherer, A Fassl, T Sinkovic, et al.  \"Apoptosis.\"  17, \"p53-dependent regulation of Mcl-1 contributes to synergistic cell death by ionizing radiation and the Bcl-2\/Bcl-XL inhibitor ABT-737.\" 187 (2012)","DOI":"10.1007\/s10495-011-0664-3"},{"key":"50","doi-asserted-by":"crossref","unstructured":"L Wang, L Lankhorst, R Bernards,  \"Nat Rev Cancer.\"  22, \"Exploiting senescence for the treatment of cancer.\" 340 (2022)","DOI":"10.1038\/s41568-022-00450-9"},{"key":"52","doi-asserted-by":"crossref","unstructured":"M Gilormini, C Malesys, E Armandy, et al.  \"Oncotarget.\"  7, \"Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC.\" 16731 (2016)","DOI":"10.18632\/oncotarget.7744"},{"key":"53","doi-asserted-by":"crossref","unstructured":"AM Pesch, BC Chandler, AR Michmerhuizen, et al.  \"Cancer Res Commun.\"  2, \"Bcl-xL inhibition radiosensitizes PIK3CA\/PTEN wild-type triple negative breast cancers with low Mcl-1 expression.\" 679 (2022)","DOI":"10.1158\/2767-9764.CRC-22-0024"},{"key":"54","doi-asserted-by":"crossref","unstructured":"MR Jackson, M Ashton, AL Koessinger, et al.  \"Int J Radiat Oncol Biol Phys.\"  106, \"Mesothelioma cells depend on the antiapoptotic protein Bcl-xL for survival and are sensitized to ionizing radiation by BH3-mimetics.\" 867 (2020)","DOI":"10.1016\/j.ijrobp.2019.11.029"},{"key":"55","doi-asserted-by":"crossref","unstructured":"N Malaquin, A Vancayseele, S Gilbert, et al.  \"Cells 2020.\"  9, \"DNA damage- but not enzalutamide-induced senescence in prostate cancer promotes senolytic Bcl-xL inhibitor sensitivity.\" 1593 (July 1)","DOI":"10.3390\/cells9071593"},{"key":"56","doi-asserted-by":"crossref","unstructured":"K Tuomainen, A Hyyti\u00e4inen, A Al-Samadi, et al.  \"Sci Rep.\"  11, \"High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma.\" 14755 (2021)","DOI":"10.1038\/s41598-021-94259-5"},{"key":"57","doi-asserted-by":"crossref","unstructured":"B Sobol, O Azzam Nieto, EL Eberlein, et al.  \"Int J Mol Sci.\"  23, \"Specific targeting of antiapoptotic Bcl-2 proteins as a radiosensitizing approach in solid tumors.\" 7850 (2022)","DOI":"10.3390\/ijms23147850"},{"key":"58","doi-asserted-by":"crossref","unstructured":"V Ritter, F Krautter, D Klein, et al.  \"Cell Death Dis.\"  12, \"Bcl-2\/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy.\" 694 (2021)","DOI":"10.1038\/s41419-021-03971-7"},{"key":"59","doi-asserted-by":"crossref","unstructured":"K Sato, S Iwasaki, H Yoshino,  \"Int J Mol Sci.\"  22, \"Effects and related mechanisms of the senolytic agent ABT-263 on the survival of irradiated A549 and Ca9-22 cancer cells.\" 13233 (2021)","DOI":"10.3390\/ijms222413233"},{"key":"61","doi-asserted-by":"crossref","unstructured":"D Revskij, A Woitas, B K\u00f6lle, et al.  \"Hepatobiliary Pancreat Dis Int.\"  23, \"Effects of triggers of senescence and senolysis in murine pancreatic cancer cells.\" 628 (2024)","DOI":"10.1016\/j.hbpd.2024.06.001"},{"key":"62","doi-asserted-by":"crossref","unstructured":"K Korelin, M Oostveen, W Wahbi, et al.  \"Biomed Pharmacother Biomedecine Pharmacother.\"  175, \"Evaluation of BH3 mimetics as a combination therapy with irradiation in head and neck squamous cell carcinoma.\" 116719 (2024)","DOI":"10.1016\/j.biopha.2024.116719"},{"key":"63","doi-asserted-by":"crossref","unstructured":"K Suzuki, K Kawamura, R Ujiie, et al.  \"Mutat Res Genet Toxicol Environ Mutagen.\"  876\u2013877, \"Characterization of 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models.\" 4975 (2016)","DOI":"10.3892\/ol.2016.5345"},{"key":"67","doi-asserted-by":"crossref","unstructured":"S Khozooei, K Lettau, F Barletta, et al.  \"J Exp Clin Cancer Res CR.\"  41, \"Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells.\" 256 (2022)","DOI":"10.1186\/s13046-022-02442-x"},{"key":"68","doi-asserted-by":"crossref","unstructured":"TW. Kim,  \"Int J Mol Sci.\"  24, \"Fisetin, an anti-inflammatory agent, overcomes radioresistance by activating the PERK-ATF4-CHOP axis in liver cancer.\" 9076 (2023)","DOI":"10.3390\/ijms24109076"},{"key":"69","doi-asserted-by":"crossref","unstructured":"E Fielder, T Wan, G Alimohammadiha, et al.  \"eLife.\"  11, \"Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice.\" e75492 (2022)","DOI":"10.7554\/eLife.75492"},{"key":"70","doi-asserted-by":"crossref","unstructured":"J Pan, D Li, Y Xu, et al.  \"Int J Radiat Oncol.\"  99, \"Inhibition of Bcl-2\/xl With ABT-263 selectively kills senescent type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice.\" 353 (2017)","DOI":"10.1016\/j.ijrobp.2017.02.216"},{"key":"71","doi-asserted-by":"crossref","unstructured":"H Yang, C Chen, H Chen, et al.  \"Aging 2020.\"  12, \"Navitoclax (ABT263) reduces inflammation and promotes chondrogenic phenotype by clearing senescent osteoarthritic chondrocytes in osteoarthritis.\" 12750 (July 1)","DOI":"10.18632\/aging.103177"},{"key":"72","doi-asserted-by":"publisher","unstructured":"M Schafer, T White, K Iijima,  \"Nat Commun.\"  8, \"Cellular senescence mediates fibrotic pulmonary disease.\" 14532 (2017)","DOI":"10.1038\/ncomms14532"},{"key":"73","doi-asserted-by":"crossref","unstructured":"Y Marmary, R Adar, S Gaska, et al.  \"Cancer Res.\"  76, \"Radiation-induced loss of salivary gland function is driven by cellular senescence and prevented by IL6 modulation.\" 1170 (2016)","DOI":"10.1158\/0008-5472.CAN-15-1671"},{"key":"74","doi-asserted-by":"crossref","unstructured":"L Xu, Y Wang, J Wang, et al.  \"Int J Mol Sci.\"  22, \"Radiation-induced osteocyte senescence alters bone marrow mesenchymal stem cell differentiation potential via paracrine signaling.\" 9323 (2021)","DOI":"10.3390\/ijms22179323"},{"key":"75","doi-asserted-by":"crossref","unstructured":"Y Zhu, T Tchkonia, T Pirtskhalava, et al.  \"Aging Cell.\"  14, \"The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.\" 644 (2015)","DOI":"10.1111\/acel.12344"},{"key":"76","doi-asserted-by":"crossref","unstructured":"S Patil, JL Reedy, BT Scroggins, et al.  \"Aging 2022.\"  14, \"Senescence-associated tumor growth is promoted by 12-Lipoxygenase.\" 1068 (Feb)","DOI":"10.18632\/aging.203890"},{"key":"77","doi-asserted-by":"crossref","unstructured":"A Yabluchanskiy, S Tarantini, P Balasubramanian, et al.  \"GeroScience 2020.\"  42, \"Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation-induced impairment of neurovascular coupling responses protecting cognitive function in mice.\" 409 (Apr)","DOI":"10.1007\/s11357-020-00154-8"},{"key":"78","doi-asserted-by":"crossref","unstructured":"R Gulej, \u00c1 Ny\u00fal-T'oth, C Ahire, et al.  \"GeroScience.\"  45, \"Elimination of senescent cells by treatment with Navitoclax\/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain.\" 2983 (2023)","DOI":"10.1007\/s11357-023-00870-x"},{"key":"79","doi-asserted-by":"crossref","unstructured":"X Peng, Y Wu, U Brouwer, et al.  \"Cell Death Dis.\"  11, \"Cellular senescence contributes to radiation-induced hypo-salivation by affecting the stem\/progenitor cell niche.\" 854 (2020)","DOI":"10.1038\/s41419-020-03074-9"},{"key":"81","unstructured":"A Chandra, AB Lagnado, JN Farr, et al.  \"Roles of cellular senescence in driving bone marrow adiposity in radiation- and aging-associated bone loss.\""},{"key":"82","doi-asserted-by":"crossref","unstructured":"AK Sharma, RL Roberts, RD Benson, et al.  \"Front Cell Dev Biol.\"  8, \"The senolytic drug navitoclax (ABT-263) causes trabecular bone loss and impaired osteoprogenitor function in aged mice.\" 354 (2020)","DOI":"10.3389\/fcell.2020.00354"},{"key":"83","doi-asserted-by":"publisher","unstructured":"SH Lin, H Willers, S Krishman, et al.  \"Int J Radiat Oncol Biol Phys.\"  5, \"Moving Beyond the Standard of Care: Accelerate Testing of Radiation-Drug Combinations Lin.\" 1131 (2021)","DOI":"10.1016\/j.ijrobp.2021.08.018"},{"key":"84","doi-asserted-by":"crossref","unstructured":"PGS. Prasanna,  \"Radiat Res.\"  202, \"Harnessing senescence for antitumor immunity to advance cancer treatment.\" 727 (2024)","DOI":"10.1667\/RADE-24-00098.1"},{"key":"85","doi-asserted-by":"crossref","unstructured":"Y Liu, J Pagacz, DJ Wolfgeher, et al.  \"J Immunother Cancer.\"  11, \"Senescent cancer cell vaccines induce cytotoxic T cell responses targeting primary tumors and disseminated tumor cells.\" e005862 (2023)","DOI":"10.1136\/jitc-2022-005862"},{"key":"86","doi-asserted-by":"crossref","unstructured":"D Dai, Y Pei, B Zhu, et al.  \"Cell Rep Med.\"  5, \"Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.\" 101550 (2024)","DOI":"10.1016\/j.xcrm.2024.101550"},{"key":"88","unstructured":"\"Nat Aging.\"  2, \"Consortium to map senescent cells throughout the human lifespan to understand physiological health.\" 1090 (2022)"},{"key":"90","doi-asserted-by":"crossref","unstructured":"JH Kim, SL Brown, MN Gordon,  \"Radiat Oncol Lond Engl.\"  18, \"Radiation-induced senescence: therapeutic opportunities.\" 10 (2023)","DOI":"10.1186\/s13014-022-02184-2"},{"key":"91","doi-asserted-by":"crossref","unstructured":"R Wang, Z Yu, B Sunchu, et al.  \"Aging Cell.\"  16, \"Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism.\" 564 (2017)","DOI":"10.1111\/acel.12587"},{"key":"93","doi-asserted-by":"crossref","unstructured":"Q Hu, J Peng, L Jiang, et al.  \"Cell Death Dis.\"  11, \"Metformin as a senostatic drug enhances the anticancer efficacy of CDK4\/6 inhibitor in head and neck squamous cell carcinoma.\" 925 (2020)","DOI":"10.1038\/s41419-020-03126-0"},{"key":"94","doi-asserted-by":"crossref","unstructured":"R Kendirci-Katirci, L Sati, C Celik-Ozenci,  \"J Assist Reprod Genet.\"  41, \"Deciphering the role of rapamycin in modulating decidual senescence: implications for decidual remodeling and implantation failure.\" 2441 (2024)","DOI":"10.1007\/s10815-024-03207-5"},{"key":"95","doi-asserted-by":"publisher","unstructured":"C Correia-Melo, J Birch, E Fielder, et al.  \"Aging Cell.\"  18, \"Rapamycin improves healthspan but not inflammaging in nfjb1\u2013\/\u2013 mice.\" e12882 (2019)","DOI":"10.1111\/acel.12882"},{"key":"87","doi-asserted-by":"crossref","unstructured":"E Fletcher-Sananikone, S Kanji, N Tomimatsu, et al.  \"Cancer Res.\"  81, \"Elimination of radiation-induced Senescence in the brain tumor microenvironment attenuates glioblastoma recurrence.\" 5935 (2021)","DOI":"10.1158\/0008-5472.CAN-21-0752"},{"key":"60","doi-asserted-by":"crossref","unstructured":"C Huart, M Fransolet, C Demazy, et al.  \"Cancers.\"  14, \"Taking advantage of the senescence-promoting effect of Olaparib after X-ray and proton irradiation using the senolytic drug, ABT-263.\" 1460 (2022)","DOI":"10.3390\/cancers14061460"},{"key":"11","doi-asserted-by":"crossref","unstructured":"V Gorgoulis, PD Adams, A Alimonti, et al.  \"Cell.\"  179, \"Cellular senescence: defining a path forward.\" 813 (2019)","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"80","doi-asserted-by":"crossref","unstructured":"A Chandra, AB Lagnado, JN Farr, et al.  \"J Bone Miner Res.\"  35, \"Targeted reduction of senescent cell burden alleviates focal radiotherapy-related bone loss.\" 1119 (2020)","DOI":"10.1002\/jbmr.3978"},{"key":"40","doi-asserted-by":"crossref","unstructured":"WP Roos  and B Kaina  \"Cancer Lett.\"  332, \"DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis.\" 237 (2013)","DOI":"10.1016\/j.canlet.2012.01.007"},{"key":"92","doi-asserted-by":"crossref","unstructured":"SL Brown, A Kolozsvary, DM Isrow, et al.  \"Front Oncol.\"  9, \"A novel mechanism of high dose radiation sensitization by metformin.\" 247 (2019)","DOI":"10.3389\/fonc.2019.00247"},{"key":"8","doi-asserted-by":"crossref","unstructured":"DA Gewirtz, M Alotaibi, VA Yakovlev, et al.  \"Radiat Res.\"  186, \"Tumor cell recovery from senescence induced by radiation with PARP inhibition.\" 327 (2016)","DOI":"10.1667\/RR14437.1"},{"key":"42","doi-asserted-by":"crossref","unstructured":"F Classen, P Kranz, H Riffkin, et al.  \"Exp Cell Res.\"  374, \"Autophagy induced by ionizing radiation promotes cell death over survival in human colorectal cancer cells.\" 29 (2019)","DOI":"10.1016\/j.yexcr.2018.11.004"},{"key":"9","doi-asserted-by":"crossref","unstructured":"M Alotaibi, K Sharma, T Saleh, et al.  \"Radiat Res.\"  185, \"Radiosensitization by PARP inhibition in DNA repair proficient and deficient tumor cells: Proliferative recovery in senescent cells.\" 229 (2016)","DOI":"10.1667\/RR14202.1"},{"key":"3","doi-asserted-by":"crossref","unstructured":"M Krause, A Dubrovska, A Linge, et al.  \"Adv Drug Deliv Rev.\"  109, \"Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments.\" 63 (2017)","DOI":"10.1016\/j.addr.2016.02.002"},{"key":"37","doi-asserted-by":"crossref","unstructured":"M Goldstein  and MB Kastan  \"Annu Rev Med.\"  66, \"The DNA damage response: Implications for tumor responses to radiation and chemotherapy.\" 129 (2015)","DOI":"10.1146\/annurev-med-081313-121208"},{"key":"32","doi-asserted-by":"crossref","unstructured":"MC Vozenin, J Bourhis, M Durante,  \"Nat Rev Clin Oncol.\"  19, \"Towards clinical translation of FLASH radiotherapy.\" 791 (2022)","DOI":"10.1038\/s41571-022-00697-z"},{"key":"6","doi-asserted-by":"publisher","unstructured":"D. Hanahan,  \"Cancer Discov.\"  12, \"Hallmarks of Cancer: New Dimensions.\" 31 (2022)","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"89","doi-asserted-by":"crossref","unstructured":"L Zhang, LE Pitcher, V Prahalad, et al.  \"FEBS J.\"  290, \"Targeting cellular senescence with senotherapeutics: senolytics and senomorphics.\" 1362 (2023)","DOI":"10.1111\/febs.16350"},{"key":"1","doi-asserted-by":"crossref","unstructured":"DE. Citrin,  \"N Engl J Med.\"  377, \"Recent developments in radiotherapy.\" 1065 (2017)","DOI":"10.1056\/NEJMra1608986"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/radiation-research.kglmeridian.com\/view\/journals\/rare\/aop\/article-10.1667-RADE-25-00156.1\/article-10.1667-RADE-25-00156.1.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/radiation-research.kglmeridian.com\/downloadpdf\/journals\/rare\/aop\/article-10.1667-RADE-25-00156.1\/article-10.1667-RADE-25-00156.1.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/radiation-research.kglmeridian.com\/downloadpdf\/journals\/rare\/aop\/article-10.1667-RADE-25-00156.1\/article-10.1667-RADE-25-00156.1.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:24:20Z","timestamp":1791235460000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-205\/issue-5\/RADE-25-00156.1\/Assessing-the-Complexities-of-Utilizing-BH3-Mimetics-for-a-Senolytic\/10.1667\/RADE-25-00156.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":95,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-25-00156.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}