Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors
Open accessAbstract
Purpose: Resistance to chemotherapy-induced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting Bcl-2 may provide therapeutic benefit. A phase I study of navitoclax, a novel inhibitor of Bcl-2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors. Patients and Methods: Patients enrolled to intermittent dosing cohorts received navitoclax on day −3, followed by dosing on days 1 to 14 of a 21-day cycle. Patients on continuous dosing received a 1-week lead-in dose of 150 mg followed by continuous daily administration. Blood samples were collected for pharmacokinetic analyses, biomarker analyses, and platelet monitoring. Results: Forty-seven patients, including 29 with small-cell lung cancer (SCLC) or pulmonary carcinoid, were enrolled between 2007 and 2008, 35 on intermittent and 12 on continuous dosing cohorts. Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose- and schedule-dependent thrombocytopenia was seen in all patients. One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). Pro-gastrin releasing peptide (pro-GRP) was identified as a surrogate marker of Bcl-2 amplification and changes correlated with changes in tumor volume. Conclusion: Navitoclax is safe and well tolerated, with dose-dependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of pro-GRP as a marker of treatment response will be further evaluated in phase II studies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity.
“The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
Bcl-xl inhibition with ABT263 and other small molecular inhibitors induces platelet apoptosis and results in severe thrombocytopenia, which prevents the use of ABT263 and other Bcl-xl specific inhibitors in the clinic even for cancer patients because platelets solely depend on Bcl-xl for survival.
“Bcl-xl inhibition with ABT263 and other small molecular inhibitors induces platelet apoptosis and results in severe thrombocytopenia, which prevents the use of ABT263 and other Bcl-xl specific inhibitors in the clinic—even for cancer patients—because platelets solely depend on Bcl-xl for survival24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
Both senescent cells and platelets, but not non-senescent cells, are primarily dependent on Bcl-xl for survival.
“Because both SCs and platelets, but not NCs, are primarily dependent on Bcl-xl for survival16–18,24–27 (Supplementary Fig. 1h), we evaluated the effects of PZ compared with ABT263 on the viability of WI38 NCs (Fig. 1g, left panel), IR-SCs (Fig. 1g, middle panel), and platelets (Fig. 1g, right panel).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
ABT263 is highly toxic to both WI38 IR-SCs and platelets.
“As reported, ABT263 was highly toxic to both WI38 IR-SCs (Fig. 1g, middle panel) and platelets16–18,24–27 (Fig. 1g, right panel; Supplementary Fig. 2).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
PZ can selectively induce apoptosis in senescent cells, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to non-senescent cells that are less sensitive to Bcl-xl inhibition than senescent cells.
“Therefore, PZ can selectively induce apoptosis in SCs, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to NCs that are less sensitive to Bcl-xl inhibition than SCs16–18,24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
2 retracted
Pardo, O. E., Arcaro, A., Salerno, G., Raguz, S., Downward, J., & Seckl, M. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.a115.109006 · Cited by 153 · see citing works
RetractedPardo, O. E., Arcaro, A., Salerno, G., Raguz, S., Downward, J., & Seckl, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109006200 · Cited by 145 · see citing works
RetractedAn inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407 · see citing works
ABT-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 · see citing works
Certo, M. V., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S. J., Armstrong, S. A., & Letai, A. G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.027 · Cited by 1,290 · see citing works
van Delft, M. F., Wei, A. H., Mason, K. D., Vandenberg, C. J., Chen, L., Czabotar, P. E., Willis, S. N., Scott, C. L., Day, C. L., Cory, S., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.027 · Cited by 1,237 · see citing works
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× · see citing works
“This is a mechanism-based toxicity induced by inhibition of Bcl-xL in circulating platelets,(13,18) which is required for platelet survival.(19,20) Here we describe a phase I dose-escalation study to evaluate the safety (with particular attention to platelet dynamics), pharmacokinetics, and preliminary efficacy of nav…”
BackgroundThe role of Bcl-2 family members in tumorigenesis
Kirkin, V., Joos, S., & Zörnig, M. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2003.08.009 · Cited by 555 · see citing works
Some practical improvements in the continual reassessment method for phase I studies
Goodman, S. N., ZAHURAK, M. L., & Piantadosi, S. (1995) · Statistics in Medicine · doi:10.1002/sim.4780141102 · Cited by 475 · see citing works
Bcl-2 family proteins are essential for platelet survival
Zhang, H., Nimmer, P. M., Tahir, S. K., Chen, J., Fryer, R. M., Hahn, K. R., Iciek, L. A., Morgan, S. J., Nasarre, M. C., Nelson, R., et al. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402081 · Cited by 427 · see citing works
Continual Reassessment Method: A Likelihood Approach
O’Quigley, J., & Shen, L. Z. (1996) · Biometrics · doi:10.2307/2532905 · Cited by 382 · see citing works
Bcl-2 inhibitors: small molecules with a big impact on cancer therapy
Vogler, M., Dinsdale, D. D., Dyer, M. J. S., & Cohen, G. M. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.137 · Cited by 359 · see citing works
BCL-2: Prevention of Apoptosis as a Mechanism of Drug Resistance
Reed, J. C. (1995) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(18)30104-7 · Cited by 312 · see citing works
Tahir, S. K., Yang, X., Anderson, M. G., Morgan-Lappe, S. E., Sarthy, A. V., Chen, J., Warner, R. B., Ng, S., Fesik, S. W., Elmore, S. W., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2203 · Cited by 308 · see citing works
Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors.
Brambilla, E. M., NEGOESCU, A., Gazzéri, S., Lantuéjoul, S., Moro‐Sibilot, D., Brambilla, C., & Coll, J. (1996) · Europe PMC (PubMed Central) · Cited by 268 · see citing works
Lin, X., Morgan-Lappe, S. E., Huang, X., Li, L., Zakula, D., Vernetti, L. A., Fesik, S. W., & Shen, Y. (2006) · Oncogene · doi:10.1038/sj.onc.1210166 · Cited by 245 · see citing works
Therapeutic Efficacy of ABT-737, a Selective Inhibitor of BCL-2, in Small Cell Lung Cancer
Hann, C. L., Daniel, V. C., Sugar, E. A., Dobromilskaya, I., Murphy, S. C., Cope, L., Lin, X., Hierman, J. S., Wilburn, D. L., Watkins, D. N., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5031 · Cited by 213 · see citing works
Self-citationSartorius, U., & Krammer, P. H. (2001) · International Journal of Cancer · doi:10.1002/ijc.10096 · Cited by 206 · see citing works
Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models
Shoemaker, A. R., Mitten, M. J., Adickes, J., Ackler, S., Refici, M. L., Ferguson, D. C., Oleksijew, A., O'Connor, J. M., Wang, B., Frost, D. J., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4622 · Cited by 203 · see citing works
Different forms of cell death induced by putative BCL2 inhibitors
Vogler, M., Weber, K., Dinsdale, D. D., Schmitz, I., Schulze‐Osthoff, K., Dyer, M. J. S., & Cohen, G. M. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.48 · Cited by 203 · see citing works
Rudin, C. M., Salgia, R., Wang, X., Hodgson, L. D., Masters, G. A., Green, M., & Vokes, E. E. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.3461 · Cited by 166 · see citing works
Self-citationTolcher, A. W., Chi, K., Kuhn, J. G., Gleave, M. E., Patnaik, A., Takimoto, C. H. M., Schwartz, G. H., Thompson, I. M., Berg, K., D’Aloisio, S., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2145 · Cited by 166 · see citing works
Zhang, D., & Armstrong, J. S. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402072 · Cited by 165 · see citing works
Practical implementation of a modified continual reassessment method for dose-finding trials
Piantadosi, S., Fisher, J. D., & Grossman, S. A. (1998) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050763 · Cited by 165 · see citing works
Expression of bcl‐2 oncogene protein is prevalent in small cell lung carcinomas
Jiang, S., Sato, Y., Kuwao, S., & Kameya, T. (1995) · The Journal of Pathology · doi:10.1002/path.1711770206 · Cited by 165 · see citing works
Ohmori, T., Podack, E. R., Nishio, K., Takahashi, M., Miyahara, Y., Takeda, Y., Kubota, N., Funayama, Y., Ogasawara, H., Ohira, T., et al. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1377 · Cited by 165 · see citing works
Small cell carcinomas of the lung express the Bcl-2 protein.
Ben‐Ezra, J. M., Kornstein, M. J., Grimes, M., & Krystal, G. (1994) · PubMed Central · Cited by 164 · see citing works
Distinct Angiogenic patterns are associated with high-gradein situ ductal carcinomas of the breast
Engels, K., Fox, S. B., Whitehouse, R. M., Gatter, K. C., & Harris, A. L. (1997) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199702)181:2 · Cited by 114 · see citing works
Self-citationExpression of bcl-2 — protein in small cell lung cancer
Kaiser, U., Schilli, M., Haag, U., Neumann, K., Kreipe, H. H., Коган, Е. А., & HAVEMANN, K. (1996) · Lung Cancer · doi:10.1016/0169-5002(96)00568-5 · Cited by 104 · see citing works
Cummings, J., Ward, T. H., LaCasse, E. C., Lefebvre, C. A., St-Jean, M., Durkin, J. P., Ranson, M., & Dive, C. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602363 · Cited by 76 · see citing works
Self-citationOlejniczak, E. T., Sant, C. V., Anderson, M. G., Wang, G. G., Tahir, S. K., Sauter, G., Lesniewski, R., & Semizarov, D. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0367 · Cited by 75 · see citing works
Hauck, P. M., Chao, B. H., Litz, J., & Krystal, G. W. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1118 · Cited by 72 · see citing works
Cummings, J., Ranson, M., LaCasse, E. C., Ganganagari, J. R., St-Jean, M., Jayson, G. C., Durkin, J. P., & Dive, C. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603220 · Cited by 63 · see citing works
Self-citationGraft-Versus-Host Disease of the CNS After Allogeneic Bone Marrow Transplantation
Saad, A. G., Alyea, E. P., Wen, P. Y., Girolami, U. D., & Kesari, S. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.21.7919 · Cited by 58 · see citing works
Micha, D., Cummings, J., Shoemaker, A. R., Elmore, S., Foster, K., Greaves, M. J., Ward, T. H., Rosenberg, S. H., Dive, C., & Simpson, K. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0111 · Cited by 29 · see citing works
Self-citationMoore, V. D. G., & Letai, A. G. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-1-4020-6554-5_8 · Cited by 27 · see citing works
Breton, C., Story, M. D., & Meyn, R. E. (1998) · Anti-Cancer Drugs · doi:10.1097/00001813-199810000-00002 · Cited by 12 · see citing works
Roberts, A. W., Wilson, W. S., Gandhi, L., O’Connor, O. A., Rudin, C. M., Brown, J. R., Xiong, H., Chiu, Y., Enschede, S. H., & Krivoshik, A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.3505 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058 · see citing works
Self-citationFrom basic apoptosis discoveries to advanced selective BCL-2 family inhibitors
Ashkenazi, A., Fairbrother, W. J., Leverson, J. D., & Souers, A. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.253 · Cited by 903 · see citing works
Broad targeting of resistance to apoptosis in cancer
Mohammad, R. M., Muqbil, I., Lowe, L. J., Yedjou, C. G., Hsu, H.-Y., Lin, L., Siegelin, M. D., Fimognari, C., Kumar, N. B., Dou, Q. P., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.001 · Cited by 876 · see citing works
Basu, A. B., Bodycombe, N. E., Cheah, J. H., Price, E. V., Liu, K., Schaefer, G. I., Ebright, R. Y., Stewart, M. L., Ito, D., Wang, S. Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.003 · Cited by 820 · see citing works
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Pan, R. A., Hogdal, L. J., Benito, J. M., Bucci, D. M., Han, L., Borthakur, G. M., Cortes, J. E., DeAngelo, D. J., Debose, L., Mu, H. H., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0609 · Cited by 734 · see citing works
BCL-2 family isoforms in apoptosis and cancer
Warren, C., Wong‐Brown, M. W., & Bowden, N. A. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1407-6 · Cited by 697 · see citing works
Juergens, R. A., Wrangle, J. M., Vendetti, F. P., Murphy, S. C., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C. M., Franco, N. C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0214 · Cited by 686 · see citing works
Self-citationMultiple Functions of BCL-2 Family ProteinsPreprint
Hardwick, J. M., & Soane, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008722 · Cited by 670 · see citing works
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631 · see citing works
The growing applications of SuFEx click chemistry
Barrow, A. S., Smedley, C. J., Zheng, Q., Li, S., Dong, J., & Moses, J. E. (2019) · Chemical Society Reviews · doi:10.1039/c8cs00960k · Cited by 597 · see citing works
Rudin, C. M., Hann, C. L., Garon, E. B., de Oliveira, M. R., Bonomi, P., Camidge, D. R., Chu, Q. S.-C., Giaccone, G., Khaira, D. K., Ramalingam, S. S., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3090 · Cited by 563 · see citing works
Self-citationLeverson, J. D., Phillips, D. C., Mitten, M. J., Boghaert, E. R., Diaz, D., Tahir, S. K., Belmont, L. D., Nimmer, P., Xiao, Y., Ma, X. M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa4642 · Cited by 541 · see citing works
Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes
Aguayo-Mazzucato, C., Andle, J., Lee, T. B., Midha, A., Talemal, L., Chipashvili, V., Hollister-Lock, J., van Deursen, J., Weir, G., & Bonner-Weir, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.006 · Cited by 469 · see citing works
Strategies for optimizing the response of cancer and normal tissues to radiation
Moding, E. J., Kastan, M. B., & Kirsch, D. G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4003 · Cited by 461 · see citing works
Structure-guided design of a selective BCL-XL inhibitor
Lessène, G., Czabotar, P. E., Sleebs, B. E., Zobel, K., Lowes, K. N., Adams, J. M., Baell, J. B., Colman, P. M., Deshayes, K., Fairbrother, W. J., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1246 · Cited by 381 · see citing works
Lok, B. H., Gardner, E. E., Schneeberger, V. E., Ni, A., Desmeules, P., Rekhtman, N., de Stanchina, E., Teicher, B. A., Riaz, N., Powell, S. N., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1040 · Cited by 350 · see citing works
Self-citationRecent advances in biosensor for detection of lung cancer biomarkers
Yang, G., Xiao, Z., Tang, C., Deng, Y., Huang, H., & He, Z. (2019) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2019.111416 · Cited by 331 · see citing works
Mitochondria—Judges and Executioners of Cell Death Sentences
Bhola, P. D., & Letai, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.019 · Cited by 326 · see citing works
Why do BCL-2 inhibitors work and where should we use them in the clinic?
Montero, J., & Letai, A. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.183 · Cited by 325 · see citing works
Oncogenic protein interfaces: small molecules, big challenges
Nero, T. L., Morton, C. J., Holien, J. K., Wielens, J., & Parker, M. W. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3690 · Cited by 312 · see citing works
Pathways 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 302 · see citing works
New Targetable Oncogenes in Non–Small-Cell Lung Cancer
Oxnard, G. R., Binder, A. F., & Janne, P. A. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.9829 · Cited by 299 · see citing works
Cellular Senescence in the Kidney
Docherty, M.-H., O’Sullivan, E. D., Bonventre, J. V., & Ferenbach, D. A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121251 · Cited by 291 · see citing works
BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines
Mérino, D., Kelly, G. L., Lessène, G., Wei, A. H., Roberts, A. W., & Strasser, A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.11.004 · Cited by 284 · see citing works
He, Y., Zhang, X., Chang, J., Kim, H.-N., Zhang, P., Wang, Y., Khan, S., Liu, X., Zhang, X., Lv, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15838-0 · Cited by 280 · see citing works
Targeting the B-Cell Lymphoma/Leukemia 2 Family in Cancer
Davids, M. S., & Letai, A. G. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.37.0981 · Cited by 260 · see citing works
Classification of mitocans, anti-cancer drugs acting on mitochondria
Neužil, J., Dong, L., Rohlena, J., Truksa, J., & Ralph, S. J. (2012) · Mitochondrion · doi:10.1016/j.mito.2012.07.112 · Cited by 248 · see citing works
Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives
Hafezi, S., & Rahmani, M. (2021) · Cancers · doi:10.3390/cancers13061292 · Cited by 240 · see citing works
Morelli, X., Bourgeas, R., & Roche, P. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.05.024 · Cited by 223 · see citing works
BH3 Mimetics: Status of the Field and New Developments
Billard, C. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0058 · Cited by 218 · see citing works
Akl, H., Vervloessem, T., Kiviluoto, S., Bittremieux, M., Parys, J. B., SMEDT, H. D., & Bultynck, G. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.04.017 · Cited by 216 · see citing works
Targeting Mcl-1 for the therapy of cancer
Quinn, B. A., Dash, R., Azab, B., Sarkar, S., Das, S. K., Kumar, S., Oyesanya, R. A., Dasgupta, S., Dent, P., Grant, S., et al. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.609167 · Cited by 201 · see citing works
Apoptosis in Cancer Biology and Therapy
Moyer, A. F., Tanaka, K., & Cheng, E. H. Y. (2025) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051222-115023 · Cited by 202 · see citing works
Bogenberger, J. M., Kornblau, S. M., Pierceall, W. E., Lena, R. J., Chow, D. C., Shi, C.-X., Mantei, J., Ahmann, G. J., Gonzales, I. M., Choudhary, A. K., et al. (2014) · Leukemia · doi:10.1038/leu.2014.44 · Cited by 199 · see citing works
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 199 · see citing works
Small molecule inhibitors targeting the cancers
Liu, G., Chen, T., Zhang, X., Ma, X., & Shi, H. (2022) · MedComm · doi:10.1002/mco2.181 · Cited by 198 · see citing works
Potential mechanisms of resistance to venetoclax and strategies to circumvent it
Tahir, S. K., Smith, M. L., Hessler, P., Rapp, L., Idler, K. B., Park, C. H., Leverson, J. D., & Lam, L. T. (2017) · BMC Cancer · doi:10.1186/s12885-017-3383-5 · Cited by 197 · see citing works
BH3-only proteins in apoptosis at a glance
Happo, L., Strasser, A., & Cory, S. (2012) · Journal of Cell Science · doi:10.1242/jcs.090514 · Cited by 193 · see citing works
Mérino, D., Khaw, S. L., Glaser, S. P., Anderson, D. J., Belmont, L. D., Wong, C., Yue, P., Robati, M., Phipson, B., Fairlie, W. D., et al. (2012) · Blood · doi:10.1182/blood-2011-12-400929 · Cited by 191 · see citing works
Fresquet, V., Rieger, M., Carolis, C., Garcia-Barchino, M. J., & Martinez-Climent, J. A. (2014) · Blood · doi:10.1182/blood-2014-03-560284 · Cited by 187 · see citing works
Anti-senescence compounds: A potential nutraceutical approach to healthy aging
Gurău, F., Baldoni, S., Prattichizzo, F., Espinosa, E., Amenta, F., Procopio, A. D., Albertini, M. C., Bonafè, M., & Olivieri, F. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.001 · Cited by 179 · see citing works
Current concepts in clinical radiation oncology
Orth, M., Lauber, K., Niyazi, M., Friedl, A. A., Li, M., Maihöfer, C., Schüttrumpf, L., Ernst, A., Niemoeller, O. M., & Belka, C. (2013) · Radiation and Environmental Biophysics · doi:10.1007/s00411-013-0497-2 · Cited by 177 · see citing works
Targeting Apoptosis Pathways for New Cancer Therapeutics
Bai, L., & Wang, S. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-010713-141310 · Cited by 177 · see citing works
A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers
LaBelle, J. L., Katz, S. G., Bird, G. H., Gavathiotis, E., Stewart, M. L., Lawrence, C. E., Fisher, J. K., Godes, M., Pitter, K. L., Kung, A. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci46231 · Cited by 176 · see citing works
Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy
Inoue‐Yamauchi, A., Jeng, P., Kim, K., Chen, H., Han, S., Ganesan, Y. T., Ishizawa, K., Jebiwott, S., Dong, Y., Pietanza, M. C., et al. (2017) · Nature Communications · doi:10.1038/ncomms16078 · Cited by 176 · see citing works
Walensky, L. D., & Gavathiotis, E. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.08.009 · Cited by 173 · see citing works
New Approaches to SCLC Therapy: From the Laboratory to the Clinic
Poirier, J. T., George, J., Owonikoko, T. K., Berns, A. J. M., Brambilla, E. M., Byers, L. A., Carbone, D. P., Chen, H. J., Christensen, C. L., Dive, C., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.01.016 · Cited by 173 · see citing works
Self-citationMitochondria: gatekeepers of response to chemotherapy
Sarosiek, K. A., Chonghaile, T. N., & Letai, A. G. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.08.003 · Cited by 170 · see citing works
Clinical Review: Navitoclax as a Pro-Apoptotic and Anti-Fibrotic Agent
Anuar, N. N. M., Hisam, N. S. N., Liew, S. L., & Ugusman, A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.564108 · Cited by 170 · see citing works
Direct and selective small-molecule activation of proapoptotic BAX
Gavathiotis, E., Reyna, D. E., Bellairs, J. A., Leshchiner, E. S., & Walensky, L. D. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.995 · Cited by 169 · see citing works
Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
Hu, L., Li, H., Zi, M., Li, W., Liu, J., Yang, Y., Zhou, D., Kong, Q., Zhang, Y., & He, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822816 · Cited by 167 · see citing works
Polley, E. C., Kunkel, M. W., Evans, D., Silvers, T. R., Delosh, R., Laudeman, J. A., Ogle, C., Reinhart, R. A., Selby, M. J. P., Connelly, J., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw122 · Cited by 166 · see citing works
BCL-2 inhibition in AML: an unexpected bonus?
Konopleva, M. Y., & Letai, A. G. (2018) · Blood · doi:10.1182/blood-2018-03-828269 · Cited by 164 · see citing works
Letai, A. G. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-121933 · Cited by 163 · see citing works
Kaefer, A., Yang, J., Noertersheuser, P., Mensing, S., Humerickhouse, R., Awni, W., & Xiong, H. (2014) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-014-2530-9 · Cited by 161 · see citing works
Self-citationTargeting the Bcl-2 Family in B Cell Lymphoma
Adams, C. M., Clark-Garvey, S., Porcu, P., & Eischen, C. M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2018.00636 · Cited by 158 · see citing works
Cancer therapeutics: Targeting the apoptotic pathway
Khan, K. H., Blanco-Codesido, M., & Molife, L. R. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.12.012 · Cited by 156 · see citing works
Targeting BCL2 for the Treatment of Lymphoid Malignancies
Anderson, M. A., Huang, D. C. S., & Roberts, A. W. (2014) · Seminars in Hematology · doi:10.1053/j.seminhematol.2014.05.008 · Cited by 150 · see citing works
Targeting BCL-2-like Proteins to Kill Cancer Cells
Cory, S., Roberts, A. W., Colman, P. M., & Adams, J. M. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.07.001 · Cited by 147 · see citing works
Cotargeting BCL-2 and PI3K Induces BAX-Dependent Mitochondrial Apoptosis in AML Cells
Rahmani, M., Nkwocha, J., Hawkins, E., Pei, X., Parker, R. E., Kmieciak, M., Leverson, J. D., Sampath, D., Ferreira‐Gonzalez, A., & Grant, S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3024 · Cited by 147 · see citing works
Predicting Cancer Drug Response using a Recommender System
Suphavilai, C., Bertrand, D., & Nagarajan, N. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty452 · Cited by 144 · see citing works
Cohen, N. A., Stewart, M. L., Gavathiotis, E., Tepper, J. L., Bruekner, S. R., Koss, B. S., Opferman, J. T., & Walensky, L. D. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.07.018 · Cited by 143 · see citing works
Bigos, K. J. A., Quiles, C. G., Lunj, S., Smith, D. J., Krause, M., Troost, E. G. C., West, C., Hoskin, P., & Choudhury, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1331355 · Cited by 142 · see citing works
Pan, R. A., Ruvolo, V. R., Wei, J., Konopleva, M. Y., Reed, J. C., Pellecchia, M., Andreeff, M., & Ruvolo, P. P. (2015) · Blood · doi:10.1182/blood-2014-10-604975 · Cited by 140 · see citing works
Phytochemicals As Chemosensitizers: From Molecular Mechanism to Clinical Significance
Balachandran, V., Maliekal, T. T., & Anto, R. J. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4573 · Cited by 139 · see citing works
Metabolic Heterogeneity in Patient Tumor-Derived Organoids by Primary Site and Drug Treatment
Sharick, J. T., Walsh, C. M., Sprackling, C. M., Pasch, C. A., Pham, D. L., Esbona, K., Choudhary, A., García‐Varela, R., Burkard, M. E., McGregor, S. M., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00553 · Cited by 138 · see citing works
Targeting mitochondria in cancer: current concepts and immunotherapy approaches
Pustylnikov, S., Costabile, F., Beghi, S., & Facciabene, A. (2018) · Translational research · doi:10.1016/j.trsl.2018.07.013 · Cited by 137 · see citing works
Venetoclax Is Effective in Small-Cell Lung Cancers with High BCL-2 Expression
Lochmann, T. L., Floros, K. V., Naseri, M., Powell, K. M., Cook, W., March, R. J., Stein, G. T., Greninger, P., Maves, Y. K., Saunders, L. R., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1606 · Cited by 134 · see citing works
Small-molecule Bax agonists for cancer therapy
Xin, M., Li, R., Xie, M., Park, D., Owonikoko, T. K., Sica, G., Corsino, P. E., Zhou, J., Ding, C., White, M. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms5935 · Cited by 133 · see citing works
Finally, An Apoptosis-Targeting Therapeutic for Cancer
Croce, C. M., & Reed, J. C. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1248 · Cited by 130 · see citing works
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., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411848112 · Cited by 127 · see citing works
Leverson, J. D., Sampath, D., Souers, A. J., Rosenberg, S. H., Fairbrother, W. J., Amiot, M., Konopleva, M. Y., & Letai, A. G. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0797 · Cited by 126 · see citing works
A nnexin A 2 complexes with S 100 proteins: structure, function and pharmacological manipulation
Liu, Y., Myrvang, H. K., & Dekker, L. V. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12978 · Cited by 124 · see citing works
BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells
Alford, S. E., Kothari, A., Loeff, F. C., Eichhorn, J. M., Sakurikar, N., Goselink, H. M., Saylors, R. L., Jedema, I., Falkenburg, J. H. F., & Chambers, T. C. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1849 · Cited by 124 · see citing works
BCL2 Inhibitors as Anticancer Drugs: A Plethora of Misleading BH3 Mimetics
Soderquist, R. S., & Eastman, A. R. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0031 · Cited by 124 · see citing works
Faber, A. C., Coffee, E. M., Costa, C., Dastur, A., Ebi, H., Hata, A. N., Yeo, A. T., Edelman, E. J., Song, Y., Tam, A. T., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0315 · Cited by 124 · see citing works
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment
Maggiorani, D., Lê, O., Lisi, V., Landais, S., Moquin‐Beaudry, G., Lavallée, V., Decaluwe, H., & Beausejour, C. M. (2024) · Nature Communications · doi:10.1038/s41467-024-46769-9 · Cited by 123 · see citing works
The role of apoptosis in megakaryocytes and platelets
Kile, B. T. (2014) · British Journal of Haematology · doi:10.1111/bjh.12757 · Cited by 122 · see citing works
ABT-737 is highly effective against molecular subgroups of multiple myeloma
Bodet, L., Gomez‐Bougie, P., Touzeau, C., Dousset, C., Descamps, G., Maïga, S., Avet‐Loiseau, H., Bataille, R., Moreau, P., Gouill, S. L., et al. (2011) · Blood · doi:10.1182/blood-2010-11-317438 · Cited by 121 · see citing works
Williams, M. M., & Cook, R. S. (2015) · Oncotarget · doi:10.18632/oncotarget.2792 · Cited by 120 · see citing works
Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells
Çolak, S., Zimberlin, C. D., Fessler, E., Hogdal, L. J., Prasetyanti, P. R., Grandela, C., Letai, A. G., & Medema, J. P. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.37 · Cited by 119 · see citing works
Cell death and the mitochondria: therapeutic targeting of the BCL ‐2 family‐driven pathway
Roy, M. J., Vom, A., Czabotar, P. E., & Lessène, G. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12431 · Cited by 118 · see citing works
Alam, M., Alam, S., Shamsi, A., Adnan, M., Elasbali, A. M., Al‐Soud, W. A., Alreshidi, M. M., Hawsawi, Y. M., Tippana, A., Pasupuleti, V. R., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.869672 · Cited by 118 · see citing works
Targeting BCL2-Proteins for the Treatment of Solid Tumours
Vogler, M. (2014) · Advances in Medicine · doi:10.1155/2014/943648 · Cited by 118 · see citing works
Navitoclax (ABT-263) Reduces Bcl-xL–Mediated Chemoresistance in Ovarian Cancer Models
Wong, M., Tan, N., Zha, J., Peale, F. V., Jr., Peng, Y., Fairbrother, W. J., & Belmont, L. D. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0693 · Cited by 115 · see citing works
Phillips, D. C., Xiao, Y., Lam, L. T., Litvinovich, E., Roberts-Rapp, L. A., Souers, A. J., & Leverson, J. D. (2015) · Blood Cancer Journal · doi:10.1038/bcj.2015.88 · Cited by 114 · see citing works
Self-citationLohard, S., Bourgeois, N., Maillet, L., Gautier, F., Fétiveau, A., Lasla, H., Nguyen, F., Vuillier, C., Dumont, A., Moreau‐Aubry, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13689-y · Cited by 114 · see citing works
Attacking cancer's Achilles heel: antagonism of anti‐apoptotic BCL ‐2 family members
Opferman, J. T. (2015) · FEBS Journal · doi:10.1111/febs.13472 · Cited by 113 · see citing works
Bcl-xL promotes metastasis independent of its anti-apoptotic activity
Choi, S., Chen, Z., Tang, L. H., Fang, Y., Shin, S. J., Panarelli, N. C., Chen, Y., Li, Y., Jiang, X., & Du, Y. N. (2016) · Nature Communications · doi:10.1038/ncomms10384 · Cited by 109 · see citing works
Targeting senescence as an anticancer therapy
Bousset, L., & Gil, J. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13312 · Cited by 108 · see citing works
Targeting Protein–Protein Interactions and Fragment-Based Drug Discovery
Valkov, E., Sharpe, T., Marsh, M., Greive, S., & Hyvönen, M. (2011) · Topics in Current Chemistry · doi:10.1007/128_2011_265 · Cited by 107 · see citing works
Influence of microRNAs and Long Non-Coding RNAs in Cancer Chemoresistance
Ayers, D., & Vandesompele, J. (2017) · Genes · doi:10.3390/genes8030095 · Cited by 107 · see citing works
Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer
Goodwin, C. M., Rossanese, O. W., Olejniczak, E. T., & Fesik, S. W. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.73 · Cited by 105 · see citing works
Smedley, C. J., Zheng, Q., Gao, B., Li, S., Molino, A., Duivenvoorden, H. M., Parker, B. S., Wilson, D. J. D., Sharpless, K. B., & Moses, J. E. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201813761 · Cited by 105 · see citing works
Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors
Chong, C. R., Wirth, L. J., Nishino, M., Chen, A. B., Sholl, L. M., Kulke, M. H., McNamee, C., Janne, P. A., & Johnson, B. E. (2014) · Lung Cancer · doi:10.1016/j.lungcan.2014.08.012 · Cited by 104 · see citing works
Cellular senescence and radiation-induced pulmonary fibrosis
He, Y., Thummuri, D., Zheng, G., Okunieff, P. G., Citrin, D. E., Vujašković, Ž., & Zhou, D. (2019) · Translational research · doi:10.1016/j.trsl.2019.03.006 · Cited by 104 · see citing works
The Impact of Genomic Changes on Treatment of Lung Cancer
Cardarella, S., & Johnson, B. E. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201305-0843pp · Cited by 103 · see citing works
Roberts, A. W., Advani, R. H., Kahl, B. S., Persky, D. O., Sweetenham, J. W., Carney, D. A., Yang, J., Busman, T. A., Enschede, S. H., Humerickhouse, R., et al. (2015) · British Journal of Haematology · doi:10.1111/bjh.13487 · Cited by 101 · see citing works
Self-citationTargeting Mcl-1 and other Bcl-2 family member proteins in cancer therapy
Yamaguchi, R., Lartigue, L., & Perkins, G. A. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.10.009 · Cited by 101 · see citing works
BH3-mimetics: recent developments in cancer therapy
Townsend, P. A., Kozhevnikova, M. V., Cexus, O., Zamyatnin, A. A., & Soond, S. M. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02157-5 · Cited by 101 · see citing works
- Authors
- Gandhi, L., Camidge, D. R., Ribeiro de Oliveira, M., Bonomi, P., Gandara, D., Khaira, D., Hann, C. L., McKeegan, E. M., Litvinovich, E., Hemken, P. M., Dive, C., Enschede, S. H., Nolan, C., Chiu, Y.-L., Busman, T., Xiong, H., Krivoshik, A. P., Humerickhouse, R., Shapiro, G. I., & Rudin, C. M.
- Affiliations
- Rush University Medical Center (US)
- From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-03-01
- Volume
- 29
- Issue
- 7
- Pages
- 909-916
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4668282
- OpenAlex
- W2119316461
- Cited by
- 603
- References
- 39
- Citations by year
- 2026: 35 · 2025: 28 · 2024: 30 · 2023: 34 · 2022: 32 · 2021: 37 · 2020: 39 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 40 · 2015: 46 · 2014: 57 · 2013: 54 · 2012: 51
- FWCI
- 24.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- National Cancer Institute (P30CA006973)
- 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, BCL-2 inhibitor, small cell lung cancer, bronchial carcinoid, thrombocytopenia, progastrin-releasing peptide, apoptosis resistance, pharmacokinetics, safety and tolerability, intermittent dosing, continuous dosing, surrogate markers
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Aniline Compounds, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Neoplasms, Prognosis, Sulfonamides, Survival Analysis, Treatment Outcome, Risk Assessment, Genes, bcl-2, Maximum Tolerated Dose, Small Cell Lung Carcinoma
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
