Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy

Mitochondria and Apoptosis

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Autophagy fights disease through cellular self-digestion

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Cell Death

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Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy

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An inhibitor of Bcl-2 family proteins induces regression of solid tumours

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Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells

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Live or let die: the cell's response to p53

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Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis

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ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

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Involvement of the bcl -2 Gene in Human Follicular Lymphoma

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Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics

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X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death

1996 • 1,456 citations

Bid, Bax, and Lipids Cooperate to Form Supramolecular Openings in the Outer Mitochondrial Membrane

2002 • 1,443 citations

BAX and BAK Regulation of Endoplasmic Reticulum Ca ²⁺ : A Control Point for Apoptosis

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bcl-2-Immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation

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The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized

2006 • 1,193 citations

Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells

2000 • 1,170 citations

Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak

2007 • 1,110 citations

Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1

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Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia

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BID: a novel BH3 domain-only death agonist.

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The Fas Signaling Pathway: More Than a Paradigm

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Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2

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Three-Dimensional Structure of the Apoptosome

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Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death.

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Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

2001 • 644 citations

Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis

2007 • 638 citations

Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group

2006 • 597 citations

Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737

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Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL

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Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis

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Expression of bcl-xL can confer a multidrug resistance phenotype

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Apoptosis-based therapies for hematologic malignancies

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Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML)

2003 • 335 citations

Bcl-2–family proteins and hematologic malignancies: history and future prospects

2008 • 325 citations

Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737

2007 • 302 citations

Randomized Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen Sodium (Bcl-2 antisense) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

2007 • 298 citations

Connected to Death: The (Unexpurgated) Mitochondrial Pathway of Apoptosis

2005 • 291 citations

Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release

2000 • 244 citations

A novel Bcl-2/Bcl-XL/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma

2006 • 229 citations

Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma

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Phase I to II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia

2005 • 191 citations

In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute

2008 • 189 citations

The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak

2007 • 189 citations

Randomized Phase II Study of Carboplatin and Etoposide With or Without thebcl-2Antisense Oligonucleotide Oblimersen for Extensive-Stage Small-Cell Lung Cancer: CALGB 30103

2008 • 164 citations

Bcl-2 Expression as a Predictive Marker of Hormone-Refractory Prostate Cancer Treated with Taxane-Based Chemotherapy

2006 • 163 citations

A Phase II, Pharmacokinetic, and Biological Correlative Study of Oblimersen Sodium and Docetaxel in Patients with Hormone-Refractory Prostate Cancer

2005 • 162 citations

Bodyguards and assassins: Bcl‐2 family proteins and apoptosis control in chronic lymphocytic leukaemia

2005 • 157 citations

Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo

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Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated bcl-2

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A Small-Molecule Inhibitor of Bcl-XL Potentiates the Activity of Cytotoxic DrugsIn vitroandIn vivo

2006 • 145 citations

High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate

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Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein

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The Small Organic Compound HA14-1 Prevents Bcl-2 Interaction with Bax to Sensitize Malignant Glioma Cells to Induction of Cell Death

2006 • 132 citations

Mechanism of Synergy of N-(4-Hydroxyphenyl)Retinamide and ABT-737 in Acute Lymphoblastic Leukemia Cell Lines: Mcl-1 Inactivation

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Histone Deacetylase Inhibitor Downregulation of bcl-xl Gene Expression Leads to Apoptotic Cell Death in Mesothelioma

2001 • 122 citations

Targeted therapy against Bcl-2-related proteins in breast cancer cells

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An ROS generator, antimycin A, inhibits the growth of HeLa cells via apoptosis

2007 • 106 citations

Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma

2004 • 100 citations

Phase II Study of G3139, a Bcl-2 Antisense Oligonucleotide, in Combination With Dexamethasone and Thalidomide in Relapsed Multiple Myeloma Patients

2005 • 97 citations

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

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Concomitant Inhibition of MDM2 and Bcl-2 Protein Function Synergistically Induce Mitochondrial Apoptosis in AML

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CD6 Ligation Modulates the Bcl-2/Bax Ratio and Protects Chronic Lymphocytic Leukemia B Cells From Apoptosis Induced by Anti-IgM

1997 • 90 citations

Bcl-2 Inhibitors Sensitize Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Uncoupling of Mitochondrial Respiration in Human Leukemic CEM Cells

2004 • 82 citations

A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse

2006 • 73 citations

Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions

2007 • 70 citations

sHA 14-1, a stable and ROS-free antagonist against anti-apoptotic Bcl-2 proteins, bypasses drug resistances and synergizes cancer therapies in human leukemia cell

2007 • 70 citations

Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN

2002 • 69 citations

Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy

2006 • 61 citations

Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor

2005 • 61 citations

A phase III randomized trial of intensive induction and consolidation chemotherapy ± oblimersen, a pro-apoptotic Bcl-2 antisense oligonucleotide in untreated acute myeloid leukemia patients >60 years old

2007 • 59 citations

High expression of bcl-2 is the rule in acute lymphoblastic leukemia, except in Burkitt subtype at presentation, and is not correlated with the prognosis

1994 • 58 citations

Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines

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2-Methoxy antimycin reveals a unique mechanism for Bcl-xL inhibition

2007 • 50 citations

Expression of BCL-2 proto-oncogene in adult acute lymphoblastic leukemia.

1996 • 49 citations

Intracellular glutathione levels determine cell sensitivity to apoptosis induced by the antineoplasic agent N-(4-hydroxyphenyl) retinamide.

2005 • 38 citations

A phase 1 study evaluating the safety, pharmacokinetics, and efficacy of ABT-263 in subjects with refractory or relapsed lymphoid malignancies

2008 • 35 citations

Gossypol and some other terpenoids, flavonoids, and phenols that affect quality of cottonseed protein

1979 • 31 citations

A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects with Refractory or Relapsed Lymphoid Malignancies.

2007 • 27 citations

A phase I–II study of oblimersen sodium (G3139, Genasense) in combination with doxorubicin in advanced hepatocellular carcinoma (NCI # 5798)

2007 • 21 citations

An open-label, multicenter, phase I/II study of AT-101 in combination with docetaxel (D) and prednisone (P) in men with hormone refractory prostate cancer (HRPC)

2008 • 20 citations

Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated bcl-2

1995 • 20 citations

Effect of the addition of oblimersen (Bcl-2 antisense) to fludarabine/cyclophosphamide for relapsed/refractory chronic lymphocytic leukemia (CLL) on survival in patients who achieve CR/nPR: Five-year follow-up from a randomized phase III study

2008 • 19 citations

Oblimersen and α-interferon in metastatic renal cancer: a phase II study of the California Cancer Consortium

2007 • 14 citations

Reduction in platelet counts as a mechanistic biomarker and guide for adaptive dose-escalation in phase I studies of the Bcl-2 family inhibitor ABT-263

2008 • 13 citations

A phase I trial of the small molecule pan-bcl-2 inhibitor obatoclax (GX15–070) in combination with docetaxel in patients with relapsed non-small cell lung cancer (NSCLC)

2008 • 3 citations