Cited by 895Cell death mechanisms and regulationLymphoma Diagnosis and TreatmentChronic Lymphocytic Leukemia Research

The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.

Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity

Open access

Wilson, Wyndham H, O'Connor, Owen A, Czuczman, Myron S, LaCasce, Ann S, Gerecitano, John F, Leonard, John P, Tulpule, Anil, Dunleavy, Kieron, Xiong, Hao, Chiu, Yi-Lin, Cui, Yue, Busman, Todd, Elmore, Steven W, Rosenberg, Saul H, Krivoshik, Andrew P, Enschede, Sari H, Humerickhouse, Rod A·2010·The Lancet Oncology

DOI 10.1016/s1470-2045(10)70261-8PMC PMC3025495

Open this paper in CoChat — free account

Abstract

Background Proteins of the BCL-2 family regulate clonal selection and survival of lymphocytes, and are frequently overexpressed in lymphomas. Navitoclax is a targeted high-affinity small molecule that inhibits the anti-apoptotic activity of BCL-2 and BCL-XL. We aimed to assess the safety and antitumour activity of navitoclax in patients with lymphoid tumours, and establish the drug's pharmacokinetic and pharmacodynamic profiles.Methods In this phase 1 dose-escalation study, patients (aged ≥18 years) with relapsed or refractory lymphoid malignancies were enrolled and treated at seven sites in the USA between November, 2006, and November, 2009. A modified Fibonacci 3+3 design was used to assign patients to receive oral navitoclax once daily by one of two dosing schedules: intermittently for the first 14 days of a 21-day cycle (14/21) at doses of 10, 20, 40, 80, 110, 160, 225, 315, or 440 mg/day; or continuously for 21 days of a 21-day cycle (21/21) at doses of 200, 275, 325, or 425 mg/day. Study endpoints were safety, maximum tolerated dose, pharmacokinetic profile, pharmacodynamic effects on platelets and T cells, and antitumour activity. This trial is registered with ClinicalTrials.gov, number NCT00406809.Findings 55 patients were enrolled (median age 59 years, IQR 51-67), 38 to receive the 14/21 dosing schedule, and 17 to receive the 21/21 dosing schedule. Common toxic effects included grade 1 or 2 anaemia (41 patients), infection (39), diarrhoea (31), nausea (29), and fatigue (21); and grade 3 or 4 thrombocytopenia (29), lymphocytopenia (18), and neutropenia (18). On the intermittent 14/21 schedule, dose-limiting toxic effects were hospital admissions for bronchitis (one) and pleural effusion (one), grade 3 increase in aminotransferases (one), grade 4 thrombocytopenia (one), and grade 3 cardiac arrhythmia (one). To reduce platelet nadir associated with intermittent 14/21 dosing, we assessed a 150 mg/day lead-in dose followed by a continuous 21/21 dosing schedule. On the 21/21 dosing schedule, two patients did not complete the first cycle and were excluded from assessment of dose-limiting toxic effects; dose-limiting toxic effects were grade 4 thrombocytopenia (one), grade 3 increase in aminotransferases (one), and grade 3 gastrointestinal bleeding (one). Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells. Clinical responses occurred across the range of doses and in several tumour types. Ten of 46 patients with assessable disease had a partial response, and these responders had median progression-free survival of 455 days (IQR 40-218).Interpretation Navitoclax has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity inhibition of BCL-XL and BCL-2, respectively. On the basis of these findings, a 150 mg 7-day lead-in dose followed by a 325 mg dose administered on a continuous 21/21 dosing schedule was selected for phase 2 study.Funding Abbott Laboratories, Genentech, and National Cancer Institute, National Institutes of Health.

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

Crossref · 10.1016/s1470-2045(10)70261-8

Cites

45 of 45 references verified0 citation errors · 0 not checkable

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1992) · Springer series in statistics · doi:10.1007/978-1-4612-4380-9_25 · Cited by 45,239
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
Swerdlow, S. H. (2017) · Medical Entomology and Zoology · Cited by 12,933
Cell Death
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines
Hallek, M. J., Cheson, B. D., Catovsky, D., Caligaris‐Cappio, F., Dighiero, G., Döhner, H., Hillmen, P., Keating, M. J., Montserrat, E., Rai, K. R., et al. (2008) · Blood · doi:10.1182/blood-2007-06-093906 · Cited by 3,782
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720
An 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
Self-citation
Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group.
Cheson, B. D., Horning, S., Coiffier, B., Shipp, M., Fisher, R. I., Connors, J. M., Lister, T., Vose, J., Grillo-López, A., Hagenbeek, A., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.4.1244 · Cited by 3,210
A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia
Calin, G. A., Ferracin, M., Cimmino, A., Leva, G. D., Shimizu, M., Wojcik, S. E., Iorio, M. V., Visone, R., Sever, N. İ., Fabbri, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050995 · Cited by 2,415
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
Self-citation

Show all 47 references

Sorted by citations

Items 201–300 of 895

Lessons from gain‐ and loss‐of‐function models of pro‐survival Bcl2 family proteins: implications for targeted therapy
Sochalska, M., Tuzlak, S., Egle, A., & Villunger, A. (2015) · FEBS Journal · doi:10.1111/febs.13188 · Cited by 68
Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan
Liu, Z.-J., Hoffmeister, K. M., Hu, Z., Mager, D. E., Ait‐Oudhia, S., Debrincat, M. A., Pleines, I., Josefsson, E. C., Kile, B. T., Italiano, J. E., et al. (2014) · Blood · doi:10.1182/blood-2013-06-508200 · Cited by 68
Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer
Krishnan, P. D. G., Golden, E., Woodward, E., Pavlos, N. J., & Blancafort, P. (2020) · Cancers · doi:10.3390/cancers12020259 · Cited by 66
“Phase IIa trials in patients with refractory or relapsed lymphoid malignancies [113].”
Background
Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with erlotinib in patients with advanced solid tumors
Tolcher, A. W., LoRusso, P. M., Arzt, J. A., Busman, T. A., Lian, G., Rudersdorf, N. S., Vanderwal, C. A., Kirschbrown, W. P., Holen, K. D., & Rosen, L. S. (2015) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-015-2883-8 · Cited by 68
“In addition, treatment with navitoclax was associated with encouraging disease control rates in phase I studies of patients with various solid tumors and hematologic malignancies, including relapsed/refractory CLL [23], SCLC, and other solid tumors [11].”
BackgroundMethodInfluentialSelf-citation
TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo
Karpel‐Massler, G., Bâ, M., Shu, C., Halatsch, M., Westhoff, M., Bruce, J. N., Canoll, P., & Siegelin, M. D. (2015) · Oncotarget · doi:10.18632/oncotarget.5505 · Cited by 68
A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors
Vlahovic, G., Karantza, V., Wang, D., Cosgrove, D., Rudersdorf, N. K., Yang, J., Xiong, H., Busman, T. A., & Mabry, M. H. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0116-3 · Cited by 66
“Clinical trial experience to date suggests a limited role for navitoclax as monotherapy, at least in solid tumors [9–12].”
BackgroundSelf-citation
Targeting BCL-2 in B-cell lymphomas
Davids, M. S. (2017) · Blood · doi:10.1182/blood-2017-04-737338 · Cited by 65
Local delivery of a senolytic drug in ischemia and reperfusion-injured heart attenuates cardiac remodeling and restores impaired cardiac function
Lee, J., Park, B., Park, J.-H., Lim, S., Kwon, S. P., Hwang, J., Kim, H., Park, H., & Kim, B. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.08.028 · Cited by 66
EBV BCL-2 homologue BHRF1 drives chemoresistance and lymphomagenesis by inhibiting multiple cellular pro-apoptotic proteins
Fitzsimmons, L., Cartlidge, R., Chang, C. W. T., Sejic, N., Galbraith, L. C. A., Suraweera, C. D., Croom-Carter, D. S. G., Dewson, G., Tierney, R. J., Bell, A. I., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0435-1 · Cited by 67
The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy
Cao, L., Li, K., Li, Q., Tong, Q., Wang, Y., & Huang, L. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02475-8 · Cited by 79
“However, these senolytic drugs have been reported with adverse effects as nausea, vomiting, diarrhea, fatigue, and, more importantly, even thrombocytopenia and neutropenia [332–334].”
How to unleash mitochondrial apoptotic blockades to kill cancers?
Deng, J. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.08.005 · Cited by 65
Therapeutics targeting Bcl-2 in hematological malignancies
Ruefli-Brasse, A. A., & Reed, J. C. (2017) · Biochemical Journal · doi:10.1042/bcj20170080 · Cited by 64
Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy
Mohana‐Kumaran, N., Hill, D. S., Allen, J. D., & Haass, N. K. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12242 · Cited by 63
“A number of phase I studies of single-agent navitoclax (Roberts et al., 2012; Wilson et al., 2010) or obatoclax (Hwang et al., 2010; O’Brien et al., 2009; Oki et al., 2012; Schimmer et al., 2008) showed the feasibility of targeting the BCL-2 family for anticancer therapy.”
Background
The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors
Ko, T. K., Chuah, C. T. H., Huang, J. W. J., Ng, K.-P., & Ong, S. T. (2014) · Oncotarget · doi:10.18632/oncotarget.1925 · Cited by 63
High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition
Bate-Eya, L. T., den Hartog, I. J. M., van der Ploeg, I., Schild, L. G., Köster, J., Santo, E. E., Westerhout, E. M., Versteeg, R., Caron, H. N., Molenaar, J. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8547 · Cited by 63
Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers
Azzarito, V., Miles, J. A., Fisher, J., Edwards, T. A., Warriner, S. L., & Wilson, A. J. (2015) · Chemical Science · doi:10.1039/c4sc03559c · Cited by 62
MCL-1 inhibitors – where are we now (2019)?
Fletcher, S. (2019) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1672661 · Cited by 62
“Accordingly, fragment-based and structure-based design toward BH3 mimetics have led to the discovery of the dual BCL2/BCL-xL inhibitor ABT-263 [5] (navitoclax) whose clinical success was thwarted through the induction of thrombocytopenia as a consequence of the inhibition of BCL-xL in platelets [6].”
Background
Differential expression of miR-17∼92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia
Scherr, M., Elder, A., Battmer, K., Barzan, D., Bomken, S. N., Ricke‐Hoch, M., Schröder, A., Venturini, L., Blair, H., Vormoor, J. H., et al. (2013) · Leukemia · doi:10.1038/leu.2013.361 · Cited by 61
The Role of Lymphatic Transport on the Systemic Bioavailability of the Bcl-2 Protein Family Inhibitors Navitoclax (ABT-263) and ABT-199
Choo, E. F., Boggs, J. W., Zhu, C., Lubach, J. W., Catron, N. D., Jenkins, G. J., Souers, A. J., & Voorman, R. L. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.055053 · Cited by 63
The dietary compound luteolin inhibits pancreatic cancer growth by targeting BCL-2
Li, Z., Zhang, Y., Chen, L., & Li, H. (2018) · Food & Function · doi:10.1039/c8fo00033f · Cited by 63
Anti-cancer drug discovery and development
Liu, Q., & Wang, H. (2012) · Communicative & Integrative Biology · doi:10.4161/cib.21554 · Cited by 63
Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance
Pécot, J., Maillet, L., Pen, J. L., Vuillier, C., Trécesson, S. D. C., Fétiveau, A., Sarosiek, K. A., Bock, F. J., Braun, F., Letai, A. G., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.064 · Cited by 68
“The on-target doselimiting effects of BH3 mimetics on platelet survival indicate that pharmacological inhibition of BCL-xL can be achieved by these compounds in vivo (Wilson et al., 2010).”
Background
Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas
Koch, R., Christie, A. L., Crombie, J. L., Palmer, A. C., Plana, D., Shigemori, K., Morrow, S. N., Scoyk, A. V., Wu, W., Brem, E. A., et al. (2018) · Blood · doi:10.1182/blood-2018-07-865527 · Cited by 60
Mechanisms of venetoclax resistance and solutions
Liu, J., Chen, Y., Yu, L., & Yang, L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1005659 · Cited by 60
Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker
Richard, D. J., Lena, R. J., Bannister, T. D., Blake, N., Pierceall, W. E., Carlson, N. E., Keller, C. E., Koenig, M., He, Y., Minond, D., et al. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.08.017 · Cited by 60
Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy
Deng, J., Paulus, A., Fang, D. D., Manna, A., Wang, G., Wang, H., Zhu, S., Chen, J., Min, P., Yin, Y., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-4037 · Cited by 59
Molecular Cell Biology of Apoptosis and Necroptosis in Cancer
Dillon, C. P., & Green, D. R. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-39406-0_1 · Cited by 62
The BH3-mimetic ABT-737 sensitizes human melanoma cells to apoptosis induced by selective BRAF inhibitors but does not reverse acquired resistance
Wroblewski, D., Mijatov, B., Mohana‐Kumaran, N., Lai, F., Gallagher, S. J., Haass, N. K., Zhang, X. D., & Hersey, P. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs330 · Cited by 60
Autofluorescence Imaging of Treatment Response in Neuroendocrine Tumor Organoids
Gillette, A. A., Babiarz, C. P., VanDommelen, A. R., Pasch, C. A., Clipson, L. J., Matkowskyj, K. A., Deming, D. A., & Skala, M. C. (2021) · Cancers · doi:10.3390/cancers13081873 · Cited by 57
BCL-xL inhibition potentiates cancer therapies by redirecting the outcome of p53 activation from senescence to apoptosis
Bharti, V., Watkins, R., Kumar, A., Shattuck-Brandt, R. L., Mossing, A., Mittra, A., Shen, C., Tsung, A., Davies, A. E., Hanel, W. G., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111826 · Cited by 60
Small Molecule Inhibition of the TNF Family Cytokine CD40 Ligand through a Subunit Fracture Mechanism
Silvian, L. F., Friedman, J. E., Strauch, K., Cachero, T. G., Day, E. S., Qian, F., Cunningham, B. C., Fung, A. D., Sun, L., Su, L., et al. (2011) · ACS Chemical Biology · doi:10.1021/cb2000346 · Cited by 57
“Despite many attempts involving a wide range of PPI targets, if special cases such as integrins, proteinases and GPCRs are excluded then only a relatively small number of PPI inhibitors have been reported and, with the exception of some complex natural products (5), in only a handful of cases has a synthetic inhibitor…”
Background
Wnt5a and ROR1 activate non-canonical Wnt signaling via RhoA in TCF3-PBX1 acute lymphoblastic leukemia and highlight new treatment strategies via Bcl-2 co-targeting
Karvonen, H., Perttilä, R., Niininen, W., Hautanen, V., Barker, H. R., Murumägi, A., Heckman, C. A., & Ungureanu, D. (2019) · Oncogene · doi:10.1038/s41388-018-0670-9 · Cited by 57
Cytoplasmic chromatin fragments-from mechanisms to therapeutic potential.
Miller, K. N., Dasgupta, N., Liu, T., Adams, P. D., & Vizioli, M. G. (2021) · eLife · doi:10.7554/elife.63728 · Cited by 55
Nanoencapsulation of ABT-737 and camptothecin enhances their clinical potential through synergistic antitumor effects and reduction of systemic toxicity
Schmid, D., Jarvis, G. E., Fay, F., Small, D. M., Greene, M. K., Majkut, J., Spence, S., McLaughlin, K. M., McCloskey, K. D., Johnston, P. G., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.413 · Cited by 56
Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer
Banerjee, P., Kotla, S., Velatooru, L. R., Abe, R. J., Olmsted‐Davis, E. A., Cooke, J. P., Schadler, K., Deswal, A. M., Herrmann, J., Lin, S. H., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.763930 · Cited by 55
Why anti-Bcl-2 clinical trials fail: a solution
Harazono, Y., Nakajima, K., & Raz, A. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9450-8 · Cited by 57
Venetoclax for the treatment of chronic lymphocytic leukemia
Gentile, M., Petrungaro, A., Uccello, G., Vigna, E., Recchia, A. G., Caruso, N., Bossio, S., Stefano, L. D., Palummo, A., Storino, F., et al. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1386173 · Cited by 56
“However, concomitant on-target thrombocytopenia caused by BCL-XL inhibition limits the efficacy achievable with this agent [28,29].”
Background
Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions
Lawrence, M., Goyal, A., Pathak, S., & Ganguly, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137411 · Cited by 60
“Highly targeted treatments such as ABT-263, also known as the chemotherapeutic drug Navitoclax, is a BCL-2 pathway inhibitor that has been shown to cause thrombocytopenia and neutropenia under small doses [125].”
Background
ABT-737 Induces Apoptosis in Mantle Cell Lymphoma Cells with a Bcl-2 high /Mcl-1 low Profile and Synergizes with Other Antineoplastic Agents
Touzeau, C., Dousset, C., Bodet, L., Gomez‐Bougie, P., Bonnaud, S., Moreau, A., Moreau, P., Pellat‐Deceunynck, C., Amiot, M., & Gouill, S. L. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0955 · Cited by 54
Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line
Tang, Z.-H., Jiang, X., Guo, X., Fong, C. M. V., Chen, X., & Lu, J. (2016) · Oncotarget · doi:10.18632/oncotarget.13150 · Cited by 56
“So far, various ongoing trials of navitoclax alone or in combination with other drugs were being explored [37-39].”
Background
The Development and Current Use of BCL-2 Inhibitors for the Treatment of Chronic Lymphocytic Leukemia
Lampson, B. L., & Davids, M. S. (2017) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-017-0359-0 · Cited by 54
Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy
Luo, J., Sun, T., Liu, Z., Liu, Y., Liu, J., Wang, S., Shi, X., & Zhou, H. (2025) · International Journal of Oral Science · doi:10.1038/s41368-025-00380-w · Cited by 61
“168 However, senolytics do not display high enough speci ﬁ city to distinguish senescent cells from normal cells, which may lead to secondary defects such as neutropenia and thrombocytopenia, 169,170 limiting the clinical application of senolytic therapies in human diseases.”
Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo
Karpel‐Massler, G., Shu, C., Chau, L., Banu, M. A., Halatsch, M., Westhoff, M., Ramirez, Y. P., Ross, A. H., Bruce, J. N., Canoll, P., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3993 · Cited by 53
BCL2 Suppresses PARP1 Function and Nonapoptotic Cell Death
Dutta, C., Day, T. A., Kopp, N., van Bodegom, D., Davids, M. S., Ryan, J. A., Bird, L., Kommajosyula, N., Weigert, O., Yoda, A., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-4204 · Cited by 53
BH4 domain of Bcl-2 as a novel target for cancer therapy
Liu, Z., Wild, C., Ding, Y., Ye, N., Chen, H., Wold, E. A., & Zhou, J. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.11.008 · Cited by 53
“dose-limiting thrombocytopenia of navitoclax) and other off-target effects remain an issue [15].”
Background
The Structural Biology of BH3-Only Proteins
Kvansakul, M., & Hinds, M. G. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-417158-9.00003-0 · Cited by 55
“BH3-only mimics, such as ABT-737 (Oltersdorf et al., 2005) and its clinical homologs ABT-263 (Navitoclax) (Wilson et al., 2010) and ABT-199 (Souers et al., 2013) (Fig.”
Background
Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade
Williams, M. M., Lee, L., Hicks, D. J., Joly, M. M., Elion, D. L., Rahman, B., McKernan, C., Sanchez, V. M., Balko, J. M., Stricker, T. P., et al. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0280-t · Cited by 55
Critical View of Novel Treatment Strategies for Glioblastoma: Failure and Success of Resistance Mechanisms by Glioblastoma Cells
Burster, T., Traut, R., Yermekkyzy, Z., Mayer, K., Westhoff, M., Bischof, J., & Knippschild, U. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.695325 · Cited by 51
Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner
Schwab, N., Taskina, D., Leung, E., Innes, B. T., Bader, G. D., & Hazrati, L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1027116 · Cited by 56
Non-apoptotic functions of caspases in myeloid cell differentiation
Solier, S., Fontenay, M., Vainchenker, W., Droin, N. M., & Solary, É. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.19 · Cited by 55
Design of novel BH3 mimetics for the treatment of chronic lymphocytic leukemia
Billard, C. (2012) · Leukemia · doi:10.1038/leu.2012.88 · Cited by 51
Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer
Westaby, D., Jiménez‐Vacas, J. M., Padilha, A., Varkaris, A. S., Balk, S. P., Bono, J. S. D., & Sharp, A. (2021) · Cancers · doi:10.3390/cancers14010051 · Cited by 56
Degraders upgraded: the rise of PROTACs in hematological malignancies
Casan, J. M. L., & Seymour, J. F. (2024) · Blood · doi:10.1182/blood.2023022993 · Cited by 53
Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy
Kim, R., Kin, T., & Beck, W. T. (2024) · Cancers · doi:10.3390/cancers16050984 · Cited by 56
“…other hand, navitoclax, the first BH3-mimetic drug to inhibit Bcl-2 , Bcl-xL , and Bcl-W, showed clinical efficacy in CLL patients in clinical trials, but because platelet survival is dependent on Bcl-xL, dose-limiting thrombocytopenia has hampered drug development in the clinical setting [157].”
Background
Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules
Iksen, I., Witayateeraporn, W., Hardianti, B., & Pongrakhananon, V. (2024) · Phytotherapy Research · doi:10.1002/ptr.8157 · Cited by 57
Bcl-2 expression predicts sensitivity to chemotherapy in breast cancer: a systematic review and meta-analysis
Yang, D. W., Chen, M., Wang, L., Yang, L., Liu, C., & Lu, P. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-105 · Cited by 51
Mcl-1 inhibitors: a patent review
Chen, L., & Fletcher, S. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1249848 · Cited by 51
First Report of Clinical Response to Venetoclax in Early T-Cell Precursor Acute Lymphoblastic Leukemia
Numan, Y., Alfayez, M., Maiti, A., Alvarado, Y., Jabbour, E. J., Ferrajoli, A., Konoplev, S. N., Kantarjian, H. M., & Bose, P. (2018) · JCO Precision Oncology · doi:10.1200/po.18.00127 · Cited by 51
1,2,3,4-Tetrahydroisoquinoline (THIQ) as privileged scaffold for anticancer de novo drug design
Faheem, F., Kumar, B. K., Sekhar, K. V. G. C., Chander, S., Kunjiappan, S., & Murugesan, S. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1916464 · Cited by 52
“as an inevitable consequence of BCL-XL inhibition leading to the development of selective inhibitors of BCL-2 such as venetoclax [149,151,152].”
Background
Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination
Lew, T. E., & Seymour, J. F. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01295-3 · Cited by 51
The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia
Itchaki, G., & Brown, J. R. (2016) · Therapeutic Advances in Hematology · doi:10.1177/2040620716655350 · Cited by 51
BH3 mimetics as anti-fibrotic therapy: Unleashing the mitochondrial pathway of apoptosis in myofibroblasts
Kühl, T., & Lagares, D. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.01.020 · Cited by 49
Development of a Convergent Large-Scale Synthesis for Venetoclax, a First-in-Class BCL-2 Selective Inhibitor
Ku, Y., Chan, V. S., Christesen, A. C., Grieme, T., Mulhern, M. M., Pu, Y., & Wendt, M. D. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.8b02750 · Cited by 50
Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells
Lafontaine, J., Cardin, G. B., Malaquin, N., Boisvert, J.-S., Rodier, F., & Wong, P. (2021) · Cancers · doi:10.3390/cancers13030386 · Cited by 54
Inhibition of Ceramide Metabolism Sensitizes Human Leukemia Cells to Inhibition of BCL2-Like Proteins
Casson, L. K., Howell, L. A., Mathews, L., Ferrer, M., Southall, N. T., Guha, R., Keller, J. M., Thomas, C. J., Siskind, L. J., & Beverly, L. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054525 · Cited by 49
Management of indolent lymphoma: Where are we now and where are we going
Lunning, M. A., & Vose, J. M. (2012) · Blood Reviews · doi:10.1016/j.blre.2012.09.004 · Cited by 49
Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein
Lanning, M. E., Yu, W., Yap, J. L., Chauhan, J., Chen, L., Whiting, E., Pidugu, L. S. M., Atkinson, T., Bailey, H., Li, W., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.02.006 · Cited by 50
“The specific and generic FragMap types that were used include: (1) aromatic, AROM (benzene carbons); (2) aliphatic, ALIP (propane carbons); (3) dual role hydrogen bonding atom, MEOO (methanol oxygens); (4) FORN, (formamide nitrogen); (5) FORO, (formamide oxygen); (6) IMIN, (imidazole acceptor nitrogen); (7) IMIH, (imi…”
Method
Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy
Kelly, G. L., & Strasser, A. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033510 · Cited by 50
“…of genes encoding proapoptotic BCL-2 family members has also been observed in diverse cancers, including loss of BIM in mantle cell B lymphoma (Tagawa et al. 2005) and renal cell carcinoma (Zantl et al. 2007) or loss of BAX in DNA mismatch repair–defective colon cancer (Rampino et al. 1997).”
Background
Phase IB Study of Osimertinib in Combination with Navitoclax in EGFR -mutant NSCLC Following Resistance to Initial EGFR Therapy (ETCTN 9903)
Bertino, E. M., Gentzler, R. D., Clifford, S. E., Kolesar, J., Muzikansky, A., Haura, E. B., Piotrowska, Z., Camidge, D. R., Stinchcombe, T. E., Hann, C. L., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4084 · Cited by 48
“At doses above 150 mg, a navitoclax lead-in dose of 150 mg daily for 7 days was included prior to escalation to permit stabilization of platelet levels, which are known to drop during this lead-in period (11, 12).”
BackgroundMethod
Patient-centric design for peptide delivery: Trends in routes of administration and advancement in drug delivery technologies
Ganesh, A. N., Heusser, C., Garad, S., & Sánchez-Félix, M. V. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100079 · Cited by 49
ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells
Cristofanon, S., & Fulda, S. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.163 · Cited by 48
Targeting Bcl-2/Bcl-XL Induces Antitumor Activity in Uveal Melanoma Patient-Derived Xenografts
Némati, F., de Montrion, C., Lang, G., Kraus‐Berthier, L., Carita, G., Sastre‐Garau, X., Berniard, A., Vallerand, D., Geneste, O., de Plater, L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0080836 · Cited by 49
“As relatively few clinical studies using these new compounds have been reported [26,27], no randomized clinical data are already available.”
Background
Targeting Cell Survival Proteins for Cancer Cell Death
Pandey, M. K., Prasad, S., Tyagi, A. K., Deb, L., Huang, J. M., Karelia, D. N., Amin, S., & Aggarwal, B. B. (2016) · Pharmaceuticals · doi:10.3390/ph9010011 · Cited by 50
Overcoming Resistance of Human Non-Hodgkin’s Lymphoma to CD19-CAR CTL Therapy by Celecoxib and Histone Deacetylase Inhibitors
Torres‐Collado, A. X., & Jazirehi, A. R. (2018) · Cancers · doi:10.3390/cancers10060200 · Cited by 48
“Numerous additional clinical trials have resulted in partial or complete remissions in CLL, B cell ALL, and NHL receiving autologous CD19-redirected CAR T cells.”
BackgroundInfluential
The Role of Inhibition of Apoptosis in Acute Leukemias and Myelodysplastic Syndrome
McBride, A., Houtmann, S., Wilde, L. R., Vigil, C. E., Eischen, C. M., Kasner, M. T., & Palmisiano, N. D. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00192 · Cited by 49
Physiological restraint of Bak by Bcl-x L is essential for cell survivalPreprint
Lee, E. F., Grabow, S., Chappaz, S., Dewson, G., Hockings, C., Kluck, R. M., Debrincat, M. A., Gray, D. H. D., Witkowski, M. T., Evangelista, M., et al. (2016) · Genes & Development · doi:10.1101/gad.279414.116 · Cited by 48
Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia
Saliba, A. N., John, A. J., & Kaufmann, S. H. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.95 · Cited by 47
“However, navitoclax also displayed dose-limiting thrombocytopenia([123,124]) that was traced to involvement of BCLXL in platelet survival ([125]).”
Background
Pharmacological Targeting of Senescence with Senolytics as a New Therapeutic Strategy for Neurodegeneration
Richardson, M., & Richardson, D. R. (2023) · Molecular Pharmacology · doi:10.1124/molpharm.123.000803 · Cited by 48
Bh3 induced conformational changes in B cl‐ X l revealed by crystal structure and comparative analysis
Rajan, S. S., Choi, M., Baek, K., & Yoon, H. S. (2015) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24816 · Cited by 50
Targeting the mitochondrial apoptotic pathway: a preferred approach in hematologic malignancies?
Brinkmann, K., & Kashkar, H. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.61 · Cited by 47
“However, owing to the crucial role of Bcl-xl in platelet homeostasis(34) the therapeutic use of ABT-263 was associated with transient thrombocytopenia in preclinical trials.(142) Based on the results obtained by ABT-737 and ABT-263, Abbott Laboratories has recently developed a high-affinity Bcl-2-selective BH3 mimetic…”
Background
Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy
Liu, Y., & Chen, Q. (2020) · Current Molecular Biology Reports · doi:10.1007/s40610-020-00141-0 · Cited by 41
Targeting the anti-apoptotic Bcl-2 family proteins: machine learning virtual screening and biological evaluation of new small molecules
Valentini, E., D’Aguanno, S., Martile, M. D., Montesano, C., Ferraresi, V., Patsilinakos, A., Sabatino, M., Antonini, L., Chiacchiarini, M., Valente, S., et al. (2022) · Theranostics · doi:10.7150/thno.64233 · Cited by 46
Can Drug Repurposing Accelerate Precision Oncology?
Schipper, L. J., Zeverijn, L. J., Garnett, M. J., & Voest, E. E. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0612 · Cited by 52
Therapeutic advancements in targeting BCL-2 family proteins by epigenetic regulators, natural, and synthetic agents in cancer
Sarkar, A., Paul, A., Banerjee, T., Maji, A., Saha, S., Bishayee, A., & Maity, T. K. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175588 · Cited by 47
Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk and Kill Cancer Stem Cells
Mukherjee, N., Schwan, J. V., Fujita, M., Norris, D. A., & Shellman, Y. G. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.145 · Cited by 46
“Currently ABT-263 (navitoclax) and ABT-199 are in clinical trials, with encouraging preliminary results (Gandhi et al., 2011; Roberts et al., 2012; Wilson et al., 2010).”
Background
Radiosensitization by a novel Bcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer
Loriot, Y., Mordant, P., Dugué, D., Geneste, O., Gombos, A., Opolon, P., Guégan, J., Perfettini, J., Pierré, A., Kraus‐Berthier, L., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.365 · Cited by 46
Double-hit lymphomas: current paradigms and novel treatment approaches
Dunleavy, K. M. (2014) · Hematology · doi:10.1182/asheducation-2014.1.107 · Cited by 46
Self-citation
Chemical Strategies for the Detection and Elimination of Senescent Cells
García-Fleitas, J., García‐Fernández, A., Martí‐Centelles, V., Sancenón, F., Bernardos, A., & Martínez‐Máñez, R. (2024) · Accounts of Chemical Research · doi:10.1021/acs.accounts.3c00794 · Cited by 46
Venetoclax: Targeting BCL2 in Hematological Cancers
Scheffold, A., Jebaraj, B. M. C., & Stilgenbauer, S. (2018) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-319-91439-8_11 · Cited by 45
Treatment strategies for aggressive lymphomas: what works?
Wilson, W. H. (2013) · Hematology · doi:10.1182/asheducation-2013.1.584 · Cited by 44
Self-citation
Pharmacokinetic Interaction of Rifampicin with Oral Versus Intravenous Anticancer Drugs: Challenges, Dilemmas and Paradoxical Effects Due to Multiple Mechanisms
Srinivas, N. R. (2016) · Drugs in R&D · doi:10.1007/s40268-016-0133-0 · Cited by 44
“Navitoclax represents a novel first-in-class small-molecule drug that has a high inhibitory affinity to the Bcl-2 family of receptors [20].”
Background
Overview of BCL-2 Family Proteins and Therapeutic Potentials
Huska, J. D., Lamb, H. M., & Hardwick, J. M. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8861-7_1 · Cited by 44
Venetoclax in acute myeloid leukemia – current and future directions
Lachowiez, C. A., Dinardo, C. D., & Konopleva, M. Y. (2020) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2020.1719098 · Cited by 44
Venetoclax Resistance in Acute Myeloid Leukemia
Garciaz, S., Collette, Y., & Vey, N. (2024) · Cancers · doi:10.3390/cancers16061091 · Cited by 45
“…of the treatment Although ABT-263 (navitoclax) showed promising results in phase I studies, the dose limiting toxicity of the treatment was thrombocytopenia, as BCL-XL is essential for mature platelet survival [15]. was thrombocytopenia as BCL-XL is essential for mature platelet survival [15].”
Background
New molecular targets in mantle cell lymphoma
Parekh, S. S., Weniger, M. A., & Wiestner, A. U. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.09.008 · Cited by 43
Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: In vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737
Ishitsuka, K., Kunami, N., Katsuya, H., Nogami, R., Ishikawa, C., Yotsumoto, F., Tanji, H., Mori, N., Takeshita, M., Miyamoto, S., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.11.030 · Cited by 42
Targeting Cellular Senescence for Age-Related Diseases: Path to Clinical Translation
Wyles, S. P., Tchkonia, T., & Kirkland, J. L. (2021) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000009669 · Cited by 42
Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial
Ailawadhi, S., Chen, Z., Huang, B., Paulus, A., Collins, M. C., Fu, L., Li, M., Ahmad, M., Men, L., Wang, H., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-3321 · Cited by 42
Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia
Mitchell, W. B., Pinheiro, M. D. O., Boulad, N., Kaplan, D. R., Edison, M. N., Psaila, B., Karpoff, M. N., White, M. J., Josefsson, E. C., Kile, B. T., et al. (2014) · American Journal of Hematology · doi:10.1002/ajh.23832 · Cited by 42
“Pharmacological inhibition of Bcl-xL with the BH3 mimetic drugs such as ABT-737 [9] or ABT-263 (Navitoclax) [10] triggers platelet death [6,11–14] and thrombocytopenia in mice [6,15], dogs [14], and humans [16,17].”
Background
Precision Treatment of Distinct Molecular Subtypes of Diffuse Large B-cell Lymphoma: Ascribing Treatment Based on the Molecular Phenotype
Dunleavy, K. M., Roschewski, M. J., & Wilson, W. H. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0497 · Cited by 42
“Several specific inhibitors of BCL2, such as navitoclax and ABT-199, are in development (86).”
BackgroundSelf-citation

Safety and efficacy of navitoclax, a BCL-2 and BCL-X L inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study
de Vos, S., Leonard, J. P., Friedberg, J. W., Zain, J. M., Dunleavy, K. M., Humerickhouse, R. A., Hayslip, J. W., Pesko, J. C., & Wilson, W. H. (2020) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2020.1845332 · Cited by 95
Self-citation
Navitoclax (ABT-263) Plus Rituximab: Interim Results of a Phase 1 Study In Patients with CD20-Positive Lymphoid Malignancies
Kahl, B. S., Roberts, A. W., Seymour, J. F., Advani, R. H., Persky, D. O., Yang, J., Cui, Y., Busman, T. A., Krivoshik, A., Enschede, S. H., et al. (2010) · Blood · doi:10.1182/blood.v116.21.3943.3943 · Cited by 8
Self-citation
Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL 2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD 20+ lymphoid malignancies
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
Self-citation
Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease
Roberts, 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
Self-citation
Navitoclax (ABT-263) Plus Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR): A Phase 1 Study In Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Kipps, T. J., Wierda, W. G., Jones, J. A., Swinnen, L. J., Yang, J., Cui, Y., Busman, T. A., Krivoshik, A., Enschede, S. H., & Humerickhouse, R. A. (2010) · Blood · doi:10.1182/blood.v116.21.2455.2455 · Cited by 6
Self-citation

See all

Authors: Wilson, W. H., O'Connor, O. A., Czuczman, M. S., LaCasce, A. S., Gerecitano, J. F., Leonard, J. P., Tulpule, A., Dunleavy, K., Xiong, H., Chiu, Y.-L., Cui, Y., Busman, T., Elmore, S. W., Rosenberg, S. H., Krivoshik, A. P., Enschede, S. H., & Humerickhouse, R. A.
Affiliations: National Institutes of Health (US)
Roswell Park Comprehensive Cancer Center (US)
Dana-Farber Cancer Institute (US)
Memorial Sloan Kettering Cancer Center (US)
Cornell University (US)
University of Southern California (US)
Abbott (United States) (US)
Corresponding author: Wilson, Wyndham H
ORCID: Wilson, Wyndham H
LaCasce, Ann S
Gerecitano, John F
Leonard, John P
Dunleavy, Kieron
Xiong, Hao
Chiu, Yi-Lin
Cui, Yue
Venue: The Lancet Oncology
Publisher: Elsevier BV
Published: 2010-12
Volume: 11
Issue: 12
Pages: 1149-1159
ISSN: 1470-2045 (ISSN-L)
DOI: 10.1016/s1470-2045(10)70261-8
PMC: PMC3025495
OpenAlex: W2150680216
Cited by: 876
References: 47
Citations by year: 2026: 44 · 2025: 58 · 2024: 66 · 2023: 49 · 2022: 66 · 2021: 69 · 2020: 70 · 2019: 43 · 2018: 42 · 2017: 53 · 2016: 52 · 2015: 63 · 2014: 60 · 2013: 55 · 2012: 50
FWCI: 18.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The Lancet Oncology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Abbott Fund
Abbott Laboratories
National Institutes of Health
National Cancer Institute (ZIABC010716)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Keywords: navitoclax, BCL-2 inhibitor, Bcl-xL, lymphoid malignancies, relapsed/refractory lymphoma, dose-limiting toxicity, thrombocytopenia, neutropenia, anemia, pharmacokinetics, pharmacodynamics, T cell proliferation, platelet function, antitumour activity, intermittent dosing
MeSH terms: Aged, Aniline Compounds, Antineoplastic Agents, Blood Platelets, Dosage Forms, Humans, Lymphoma, Middle Aged, Sulfonamides, T-Lymphocytes, Survival Analysis, Drug Delivery Systems, Proto-Oncogene Proteins c-bcl-2, Maximum Tolerated Dose

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

Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks