ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Integrating network toxicology, machine learning, and single-cell sequencing systems to analyze autophagy core genes in lung adenocarcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer.British journal of cancer · 2026Article
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Article
- Bioinformatics analysis identifies AURKB as a prognostic biomarker across multiple human cancers.Discover oncology · 2026Article
- Advanced and underlying therapeutic strategies in transformed small cell lung cancer.Frontiers in medicine · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- From Fibrosis to Malignancy: Mechanistic Intersections Driving Lung Cancer Progression.Cancers · 2025Review
- Immunotherapy for small cell lung cancer: current challenges and prospects.Experimental hematology & oncology · 2025Review
- Challenges of small cell lung cancer heterogeneity and phenotypic plasticity.Nature reviews. Cancer · 2025Review
- Molecular Subtypes and Targeted Therapeutic Strategies in Small Cell Lung Cancer: Advances, Challenges, and Future Perspectives.Molecules (Basel, Switzerland) · 2025Review
- Review
- Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells.Cell death & disease · 2025Article
- In-silico pharmacological insights into the therapeutic potential of microRNAs for microplastic-associated cancers.Frontiers in cell and developmental biology · 2025Review
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- Review
- Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity.Trends in cancer · 2024Review
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
purposeTherapeutic resistance to frontline therapy develops rapidly in small cell lung cancer (SCLC). Treatment options are also limited by the lack of targetable driver mutations. Therefore, there is an unmet need for developing better therapeutic strategies and biomarkers of response. Aurora kinase B (AURKB) inhibition exploits an inherent genomic vulnerability in SCLC and is a promising therapeutic approach. Here, we identify biomarkers of response and develop rational combinations with AURKB inhibition to improve treatment efficacy. EXPERIMENTAL
designSelective AURKB inhibitor AZD2811 was profiled in a large panel of SCLC cell lines (n = 57) and patient-derived xenograft (PDX) models. Proteomic and transcriptomic profiles were analyzed to identify candidate biomarkers of response and resistance. Effects on polyploidy, DNA damage, and apoptosis were measured by flow cytometry and Western blotting. Rational drug combinations were validated in SCLC cell lines and PDX models.
resultsAZD2811 showed potent growth inhibitory activity in a subset of SCLC, often characterized by, but not limited to, high cMYC expression. Importantly, high BCL2 expression predicted resistance to AURKB inhibitor response in SCLC, independent of cMYC status. AZD2811-induced DNA damage and apoptosis were suppressed by high BCL2 levels, while combining AZD2811 with a BCL2 inhibitor significantly sensitized resistant models. In vivo, sustained tumor growth reduction and regression was achieved even with intermittent dosing of AZD2811 and venetoclax, an FDA-approved BCL2 inhibitor.
conclusionsBCL2 inhibition overcomes intrinsic resistance and enhances sensitivity to AURKB inhibition in SCLC preclinical models.
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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.