The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer
Open accessAbstract
Significance: Small-cell lung cancer (SCLC) is an aggressive carcinoma with few effective treatment options beyond first-line chemotherapy. BH3 mimetics, such as ABT-263, promote apoptosis in SCLC cell lines, but early phase clinical trials demonstrated no significant clinical benefit. Here, we examine the sensitivity of a large panel of cancer cell lines, including SCLC, to ABT-263 and find that high Bcl2-interacting mediator of cell death (BIM) and low myeloid cell leukemia 1 (MCL-1) expression together predict sensitivity. SCLC cells relatively resistant to ABT-263 are sensitized by TORC1/2 inhibition via MCL-1 reduction. Combination of ABT-263 and TORC1/2 inhibition stabilizes or shrinks tumors in xenograft models, in autochthonous SCLC tumors in a genetically engineered mouse model, and in a patient-derived xenograft SCLC model. Collectively, these data support a compelling new therapeutic strategy for treating SCLC.
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“There is a growing body of evidence suggesting that deficient apoptosis induction following targeted therapy treatments can lead to a lack of efficacy”
From Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in KRASG12C -mutant Colorectal Cancer (2023) · cites this paper as [38]
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Cites
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
Systematic identification of genomic markers of drug sensitivity in cancer cells
Garnett, M. J., Edelman, E. J., Heidorn, S. J., Greenman, C. D., Dastur, A., Lau, K. W., Greninger, P., Thompson, I. R., Luo, X., Soares, J., et al. (2012) · Nature · doi:10.1038/nature11005 · Cited by 2,456
Self-citationABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Peifer, M., Fernandez‐Cuesta, L., Sos, M. L., George, J., Seidel, D., Kasper, L. H., Plenker, D., Leenders, F., Sun, R., Zander, T., et al. (2012) · Nature Genetics · doi:10.1038/ng.2396 · Cited by 1,404
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Programmed Anuclear Cell Death Delimits Platelet Life Span
Mason, K. D., Carpinelli, M. R., Fletcher, J. I., Collinge, J. E., Hilton, A. A., Ellis, S., Kelly, P. N., Ekert, P. G., Metcalf, D., Roberts, A. W., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.037 · Cited by 1,031 · cited 1×
“ABT-263 was well tolerated in the clinic with a dose-limiting toxicity of thrombocytopenia (22), an on-target toxicity of BCL-XL inhibition (23).”
BackgroundRoberts, A. W., Seymour, J. F., Brown, J. R., Wierda, W. G., Kipps, T. J., Khaw, S. L., Carney, D. A., He, S., Huang, D. C. S., Xiong, H., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.7898 · Cited by 855
Choo, A. Y., Yoon, S.-O., Kim, S. G., Roux, P. P., & Blenis, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809136105 · Cited by 829
Chresta, C. M., Davies, B. R., Hickson, I., Harding, T., Cosulich, S., Critchlow, S. E., Vincent, J. P., Ellston, R., Jones, D., Sini, P., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1751 · Cited by 812
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Rudin, C. M., Brambilla, E. M., Finn, C. F., & Sage, J. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00235-0 · Cited by 1,675
The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics
Hata, A. N., Engelman, J. A., & Faber, A. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0011 · Cited by 619
“The central role of BIM in promoting apoptosis in response to targeted therapies has also been demonstrated in other targeted therapy paradigms, including HER2-amplified breast cancers (115), ALK-positive NSCLCs (116), BRAF-mutant melanomas (106), BRAF-mutant colorectal cancers (117), and PIK3CA-mutant breast cancers…”
Self-citationPathways and mechanisms of venetoclax resistance
Bose, P., Gandhi, V. V., & Konopleva, M. Y. (2017) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2017.1283032 · Cited by 311
Origins, genetic landscape, and emerging therapies of small cell lung cancerPreprint
Semenova, E. A., Nagel, R., & Berns, A. J. M. (2015) · Genes & Development · doi:10.1101/gad.263145.115 · Cited by 247
“The same model has also been used to test the efficacy of anti-apoptotic inhibitors both as single agents and in a combination regimen (Faber et al. 2015).”
BackgroundMethodRegulation of Bim in Health and Disease
Sionov, R. V., Vlahopoulos, S., & Granot, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.5492 · Cited by 233
“Small-cell lung cancer (SCLC) with high Bim expression is among the most sensitive cells to ABT-263 treatment [584].”
Background
Metadata
- Authors
- Faber, A. C., Farago, A. F., Costa, C., Dastur, A., Gomez-Caraballo, M., Robbins, R., Wagner, B. L., Rideout, W. M., Jakubik, C. T., Ham, J., Edelman, E. J., Ebi, H., Yeo, A. T., Hata, A. N., Song, Y., Patel, N. U., March, R. J., Tam, A. T., Milano, R. J., Boisvert, J. L., Hicks, M. A., Elmiligy, S., Malstrom, S. E., Rivera, M. N., Harada, H., Windle, B. E., Ramaswamy, S., Benes, C. H., Jacks, T., & Engelman, J. A.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital Cancer Center, Boston, MA 02129;
- Koch Institute for Integrative Cancer Research At MIT (US)
- Virginia Commonwealth University (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-03-03
- Volume
- 112
- Issue
- 11
- Pages
- E1288-96
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4371986
- OpenAlex
- W1981797550
- Cited by
- 127
- References
- 46
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 10 · 2022: 9 · 2021: 9 · 2020: 15 · 2019: 14 · 2018: 21 · 2017: 15 · 2016: 13 · 2015: 7
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- HHS | NIH | National Cancer Institute (2P50 CA09057, R01CA40594, R01CA137008-01, 1U54HG006097-1, P30-CA14051)
- U.S. Department of Defense (W81-XWH-13-1-0325)
- Burroughs Wellcome Fund (n/a)
- American Cancer Society (n/a)
- Uniting Against Lung Cancer (n/a)
- Lung Cancer Research Foundation (n/a)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- navitoclax, venetoclax, BH3 mimetics, small cell lung cancer, building information modeling, Mcl-1, Bcl-2, Bcl-xL, apoptosis, combination therapy, AZD8055, rapamycin, drug resistance, cancer cell line sensitivity, patient-derived xenografts, genetically engineered mouse models
- MeSH terms
- Bcl-2-Like Protein 11, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Aniline Compounds, Animals, Antineoplastic Combined Chemotherapy Protocols, Dose-Response Relationship, Drug, Genetic Engineering, Humans, Lung Neoplasms, Membrane Proteins, Morpholines, Proto-Oncogene Proteins, Remission Induction, Sulfonamides, Apoptosis, Inhibitory Concentration 50, Xenograft Model Antitumor Assays, Cell Line, Tumor, Multiprotein Complexes, Apoptosis Regulatory Proteins, Mice, Small Cell Lung Carcinoma, TOR Serine-Threonine Kinases, Myeloid Cell Leukemia Sequence 1 Protein
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