Skip to main content
Top
Published in: Targeted Oncology 3/2018

01-06-2018 | Review Article

Targeting BCL-2 in Hematologic Malignancies

Authors: Nadia Khan, Brad Kahl

Published in: Targeted Oncology | Issue 3/2018

Login to get access

Abstract

Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma.
Literature
1.
go back to reference Tsujimoto Y, Cossman J, Jaffe E, et al. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985;228:1440–3.CrossRefPubMed Tsujimoto Y, Cossman J, Jaffe E, et al. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985;228:1440–3.CrossRefPubMed
2.
go back to reference Merino D, Lok SW, Visvader JE, et al. Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. Oncogene. 2016;35:1877–87.CrossRefPubMed Merino D, Lok SW, Visvader JE, et al. Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. Oncogene. 2016;35:1877–87.CrossRefPubMed
3.
go back to reference Del Gaizo MV, Brown JR, Certo M, et al. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117:112–21.CrossRef Del Gaizo MV, Brown JR, Certo M, et al. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117:112–21.CrossRef
4.
go back to reference Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677–81.CrossRefPubMed Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677–81.CrossRefPubMed
5.
go back to reference Hauck P, Chao BH, Litz J, et al. Alterations in the Noxa/Mcl-1 axis determine sensitivity of small cell lung cancer to the BH3 mimetic ABT-737. Mol Cancer Ther. 2009;8:883–92.CrossRefPubMed Hauck P, Chao BH, Litz J, et al. Alterations in the Noxa/Mcl-1 axis determine sensitivity of small cell lung cancer to the BH3 mimetic ABT-737. Mol Cancer Ther. 2009;8:883–92.CrossRefPubMed
6.
go back to reference Kaefer A, Yang J, Noertersheuser P, et al. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia. Cancer Chemother Pharmacol. 2014;74:593–602.CrossRefPubMed Kaefer A, Yang J, Noertersheuser P, et al. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia. Cancer Chemother Pharmacol. 2014;74:593–602.CrossRefPubMed
7.
go back to reference Rudin CM, Hann CL, Garon EB, et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012;18:3163–9.CrossRefPubMedPubMedCentral Rudin CM, Hann CL, Garon EB, et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012;18:3163–9.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Wierda WG, Zelenetz AD, Gordon LI, et al. NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia, Version 1.2017. J Natl Compr Canc Netw. 2017;15:293–311.CrossRefPubMed Wierda WG, Zelenetz AD, Gordon LI, et al. NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia, Version 1.2017. J Natl Compr Canc Netw. 2017;15:293–311.CrossRefPubMed
10.
go back to reference Hanada M, Delia D. Aiello A, et al: bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. 1993;82:1820–8.PubMed Hanada M, Delia D. Aiello A, et al: bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. 1993;82:1820–8.PubMed
11.
go back to reference Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374:311–22.CrossRefPubMed Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374:311–22.CrossRefPubMed
12.
go back to reference Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17:768–78.CrossRefPubMed Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17:768–78.CrossRefPubMed
13.
go back to reference Lozanski G, Heerema NA, Flinn IW, et al. Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004;103:3278–81.CrossRefPubMed Lozanski G, Heerema NA, Flinn IW, et al. Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004;103:3278–81.CrossRefPubMed
14.
go back to reference Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27:3994–4001.CrossRefPubMed Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27:3994–4001.CrossRefPubMed
15.
go back to reference Jones J, Choi MY, Mato AR, et al. Venetoclax (VEN) Monotherapy for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapsed after or Were Refractory to Ibrutinib or Idelalisib. Blood. 2016;128:637. Jones J, Choi MY, Mato AR, et al. Venetoclax (VEN) Monotherapy for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapsed after or Were Refractory to Ibrutinib or Idelalisib. Blood. 2016;128:637.
16.
go back to reference Kovacs G, Robrecht S, Fink AM, et al. Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. J Clin Oncol. 2016;34(31):3758–65. Kovacs G, Robrecht S, Fink AM, et al. Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. J Clin Oncol. 2016;34(31):3758–65.
17.
go back to reference Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. 2017;18:230–40.CrossRefPubMedPubMedCentral Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. 2017;18:230–40.CrossRefPubMedPubMedCentral
18.
go back to reference Seymour JF, Kipps TJ, Eichhorst BF, et al. Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study. Blood. 2017;130:LBA-2.CrossRef Seymour JF, Kipps TJ, Eichhorst BF, et al. Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study. Blood. 2017;130:LBA-2.CrossRef
19.
go back to reference Hillmen P, Munir T, Rawstron A, et al. Initial Results of Ibrutinib Plus Venetoclax in Relapsed, Refractory CLL (Bloodwise TAP CLARITY Study): High Rates of Overall Response, Complete Remission and MRD Eradication after 6 Months of Combination Therapy. Blood. 2017;130:428. Hillmen P, Munir T, Rawstron A, et al. Initial Results of Ibrutinib Plus Venetoclax in Relapsed, Refractory CLL (Bloodwise TAP CLARITY Study): High Rates of Overall Response, Complete Remission and MRD Eradication after 6 Months of Combination Therapy. Blood. 2017;130:428.
20.
go back to reference Jain N, Thompson PA, Ferrajoli A, et al. Combined Venetoclax and Ibrutinib for Patients with Previously Untreated High-Risk CLL, and Relapsed/Refractory CLL: A Phase II Trial. Blood. 2017;130:429.CrossRef Jain N, Thompson PA, Ferrajoli A, et al. Combined Venetoclax and Ibrutinib for Patients with Previously Untreated High-Risk CLL, and Relapsed/Refractory CLL: A Phase II Trial. Blood. 2017;130:429.CrossRef
21.
go back to reference Park S, Davis L, Hsu P, et al. Phase II/1b Trial of Ibrutinib Plus Prednisone and Rituximab Induction Followed By Venetoclax Plus Ibrutinib Maintenance in Newly Diagnosed High-Risk Chronic Lymphocytic Leukemia. Blood. 2017;130:5351. Park S, Davis L, Hsu P, et al. Phase II/1b Trial of Ibrutinib Plus Prednisone and Rituximab Induction Followed By Venetoclax Plus Ibrutinib Maintenance in Newly Diagnosed High-Risk Chronic Lymphocytic Leukemia. Blood. 2017;130:5351.
22.
go back to reference Stilgenbauer S, Morschhauser F, Wendtner C-M, et al. Phase Ib Study (GO28440) of Venetoclax with Bendamustine/Rituximab or Bendamustine/Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia. Blood. 2016;128:4393. Stilgenbauer S, Morschhauser F, Wendtner C-M, et al. Phase Ib Study (GO28440) of Venetoclax with Bendamustine/Rituximab or Bendamustine/Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia. Blood. 2016;128:4393.
23.
go back to reference Salles GA, Boyd TE, Morschhauser F, et al. Updated Safety and Preliminary Efficacy Data from a Phase 1b Study Combining Venetoclax (GDC-0199, ABT-199) with Bendamustine/Rituximab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia. Blood. 2015;126:4.CrossRef Salles GA, Boyd TE, Morschhauser F, et al. Updated Safety and Preliminary Efficacy Data from a Phase 1b Study Combining Venetoclax (GDC-0199, ABT-199) with Bendamustine/Rituximab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia. Blood. 2015;126:4.CrossRef
25.
go back to reference Flinn IW, Gribben JG, Dyer MJS, et al. Safety, Efficacy and MRD Negativity of a Combination of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331). Blood. 2017;130:430. Flinn IW, Gribben JG, Dyer MJS, et al. Safety, Efficacy and MRD Negativity of a Combination of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331). Blood. 2017;130:430.
26.
go back to reference Flinn IW, Brunvand M, Choi MY, et al. Safety and Efficacy of a Combination of Venetoclax (GDC-0199/ABT-199) and Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331). Blood. 2015;126:494.CrossRef Flinn IW, Brunvand M, Choi MY, et al. Safety and Efficacy of a Combination of Venetoclax (GDC-0199/ABT-199) and Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331). Blood. 2015;126:494.CrossRef
27.
go back to reference Rogers KA, Huang Y, Stark A, et al. Initial Results of the Phase 2 Treatment Naive Cohort in a Phase 1b/2 Study of Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia. Blood. 2017;130:431. Rogers KA, Huang Y, Stark A, et al. Initial Results of the Phase 2 Treatment Naive Cohort in a Phase 1b/2 Study of Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia. Blood. 2017;130:431.
28.
go back to reference Jones JA, Woyach J, Awan FT, et al. Phase 1b Results of a Phase 1b/2 Study of Obinutuzmab, Ibrutinib, and Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). Blood. 2016;128:639. Jones JA, Woyach J, Awan FT, et al. Phase 1b Results of a Phase 1b/2 Study of Obinutuzmab, Ibrutinib, and Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). Blood. 2016;128:639.
29.
go back to reference Deng J, Isik E, Fernandes SM, et al. Ibrutinib Therapy Increases BCL-2 Dependence and Enhances Sensitivity to Venetoclax in CLL. Blood. 2015;126:490. Deng J, Isik E, Fernandes SM, et al. Ibrutinib Therapy Increases BCL-2 Dependence and Enhances Sensitivity to Venetoclax in CLL. Blood. 2015;126:490.
30.
go back to reference Jayappa KD, Portell CA, Gordon V, et al. Ligands That Mimic the Tissue Microenvironment of Replicating Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) Protect Ex Vivo Patient Cell Samples from the Cytotoxicity of Combined Treatment with Ibrutinib and Venetoclax (ABT-1 99). Blood. 2015;126:448. Jayappa KD, Portell CA, Gordon V, et al. Ligands That Mimic the Tissue Microenvironment of Replicating Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) Protect Ex Vivo Patient Cell Samples from the Cytotoxicity of Combined Treatment with Ibrutinib and Venetoclax (ABT-1 99). Blood. 2015;126:448.
31.
go back to reference Davids MS, Roberts AW, Seymour JF, et al. Phase I First-in-Human Study of Venetoclax in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 2017;35:826–33.CrossRefPubMedPubMedCentral Davids MS, Roberts AW, Seymour JF, et al. Phase I First-in-Human Study of Venetoclax in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 2017;35:826–33.CrossRefPubMedPubMedCentral
32.
go back to reference Zinzani PL, Topp MS, Yuen SL, et al. Phase 2 Study of Venetoclax Plus Rituximab or Randomized Ven Plus Bendamustine+Rituximab (BR) Versus BR in Patients with Relapsed/Refractory Follicular Lymphoma: Interim Data. Blood. 2016;128:617. Zinzani PL, Topp MS, Yuen SL, et al. Phase 2 Study of Venetoclax Plus Rituximab or Randomized Ven Plus Bendamustine+Rituximab (BR) Versus BR in Patients with Relapsed/Refractory Follicular Lymphoma: Interim Data. Blood. 2016;128:617.
33.
go back to reference Zelenetz AD, Salles GA, Mason KD, et al. Results of a Phase Ib Study of Venetoclax Plus R- or G-CHOP in Patients with B-Cell Non-Hodgkin Lymphoma. Blood. 2016;128:–3032. Zelenetz AD, Salles GA, Mason KD, et al. Results of a Phase Ib Study of Venetoclax Plus R- or G-CHOP in Patients with B-Cell Non-Hodgkin Lymphoma. Blood. 2016;128:–3032.
34.
go back to reference Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31:88–94.CrossRefPubMed Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31:88–94.CrossRefPubMed
35.
go back to reference Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.CrossRefPubMedPubMedCentral Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.CrossRefPubMedPubMedCentral
36.
go back to reference Casulo C, Byrtek M, Dawson KL, et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015;33:2516–22.CrossRefPubMedPubMedCentral Casulo C, Byrtek M, Dawson KL, et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015;33:2516–22.CrossRefPubMedPubMedCentral
37.
go back to reference Tam CSL, Roberts AW, Anderson MA, et al. Combination ibrutinib (Ibr) and venetoclax (Ven) for the treatment of mantle cell lymphoma (MCL): Primary endpoint assessment of the phase 2 AIM study. J Clin Oncol. 2017;35:7520. Tam CSL, Roberts AW, Anderson MA, et al. Combination ibrutinib (Ibr) and venetoclax (Ven) for the treatment of mantle cell lymphoma (MCL): Primary endpoint assessment of the phase 2 AIM study. J Clin Oncol. 2017;35:7520.
38.
go back to reference Medeiros BC, Satram-Hoang S, Hurst D, et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127–38.CrossRefPubMedPubMedCentral Medeiros BC, Satram-Hoang S, Hurst D, et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127–38.CrossRefPubMedPubMedCentral
39.
go back to reference Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discovery. 2016;6:1106–17.CrossRefPubMedPubMedCentral Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discovery. 2016;6:1106–17.CrossRefPubMedPubMedCentral
40.
go back to reference DiNardo CD, Rausch CR, Benton C, et al. Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018;93(3):401–7. DiNardo CD, Rausch CR, Benton C, et al. Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018;93(3):401–7.
41.
go back to reference DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(2):216–28. DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(2):216–28.
42.
go back to reference Punnoose EA, Leverson JD, Peale F, et al. Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models. Mol Cancer Ther. 2016;15:1132–44.CrossRefPubMed Punnoose EA, Leverson JD, Peale F, et al. Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models. Mol Cancer Ther. 2016;15:1132–44.CrossRefPubMed
43.
go back to reference Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130:2401–9.CrossRefPubMed Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130:2401–9.CrossRefPubMed
44.
go back to reference Edwards SK, Han Y, Liu Y, et al. Signaling mechanisms of bortezomib in TRAF3-deficient mouse B lymphoma and human multiple myeloma cells. Leuk Res. 2016;41:85–95.CrossRefPubMed Edwards SK, Han Y, Liu Y, et al. Signaling mechanisms of bortezomib in TRAF3-deficient mouse B lymphoma and human multiple myeloma cells. Leuk Res. 2016;41:85–95.CrossRefPubMed
45.
go back to reference Moreau P, Chanan-Khan A, Roberts AW, et al. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017;130:2392–400.CrossRefPubMed Moreau P, Chanan-Khan A, Roberts AW, et al. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017;130:2392–400.CrossRefPubMed
46.
go back to reference Montero J, Sarosiek KA, DeAngelo JD, et al. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015;160:977–89.CrossRefPubMedPubMedCentral Montero J, Sarosiek KA, DeAngelo JD, et al. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015;160:977–89.CrossRefPubMedPubMedCentral
Metadata
Title
Targeting BCL-2 in Hematologic Malignancies
Authors
Nadia Khan
Brad Kahl
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 3/2018
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0560-7

Other articles of this Issue 3/2018

Targeted Oncology 3/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine