Role of BET Inhibitors in Triple Negative Breast Cancers
Abstract
1. Introduction
2. Bromodomain and Extraterminal Domain
3. BET Inhibitors
4. Challenges
5. Future Role of Novel Drug Design and Combinatorial Therapy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Drug | Identifier # | Tumor Type | Clinical Phase | Status |
---|---|---|---|---|
MK-8628/OTX105 | NCT02259114 | NUT Midline Carcinoma | Phase IB | Completed [93] |
Non-small Cell Lung Cancer | ||||
Castrate-resistant Prostate Cancer | ||||
Pancreatic Ductal Adenocarcinoma | ||||
GSK525762 | NCT01587703 | All solid tumors, Midline | Phase 1 | Active, not recruiting |
MK-8628 | NCT02698176 | NUT Midline Carcinoma | Phase 1 | Terminated |
Non-small Cell Lung Cancer | ||||
Castrate-resistant Prostate Cancer | ||||
Pancreatic Ductal Adenocarcinoma | ||||
INCB054329 | NCT02431260 | Solid Tumors and Hematologic Malignancy | Phase 1 Phase 2 | Terminated |
Therapeutic Agents | Malignancies | Toxicities |
---|---|---|
MK-8268/OTX-015 [88] | Relapsed/refractory leukemia | diarrhea, fatigue, anorexia. Toxicities also included dysgeusia, abdominal pain, decreased clotting factor VII |
MK-8628/OTX015 [89] | Relapsed/refractory lymphoma or multiple myeloma | thrombocytopenia, neutropenia, hyponatremia; diarrhea, dysgeusia, fatigue, anemia |
MK-8628/OTX-015 [90] | NUT midline carcinoma | thrombocytopenia, nausea, dysgeusia, hyperglycemia, fatigue |
BAY1238097 [91] | Advanced solid tumors or NHL | headache, vomiting, low back pain, Recurrent headaches |
Combination Therapy | Pre-Clinical Models Tested |
---|---|
JQ1 and FLT3-TK1 [118] | Immunodeficient mice injected with OCIAML3 or MOLM13 cells |
JQ1/dBET1 and Ponatinib [119] | Colon (HCT116, HT29), breast (MCF-7, SKBR3) and ovarian (A2780, SKOV3) cancer cells |
I-BET151 and panobinostat [120] | Immunodeficient mice injected with patient-derived melanoma cells resistant to vemurafenib |
JQ1 and panobinostat [121] | Syngeneic orthotopic murine tumors, SK-N-BE (2) neuroblastoma cells |
JQ1 and romidepsin [48] | Murine tumor models of NT2/D1 and NCCIT embryonal carcinoma |
JQ1 and rapamycin [122] | Immunodeficient mice injected with MNNG/HOS osteosarcoma cells |
CPI203 and rapamycin [123] | Immunodeficient mice injected with BON-1 pancreatic neuroendocrine tumor cells |
JQ1 and trametinib [124] | Immunodeficient mice injected with ES2 ovarian clear cell carcinoma cells |
JQ1 and vemurafenib [125] | Immunodeficient mice injected with A375 melanoma cells |
JQ1 and fulvestrant [49] | Immunodeficient mice injected with tamoxifen-resistant MCF7 breast cancer cells |
I-BET151 and lapatinib [126] | Immunodeficient mice injected with Her2þ BT474 breast cancer cells |
JQ1 and lenalidomide [127] | Immunodeficient mice injected with BC-3 lymphoma cells |
JQ1 and unidentified PD-1 inhibitor [128] | KRASmt NSCLC murine tumor model |
RVX2135 and ATR inhibitor AZ20 [129] | Syngeneic λ820 and λ2749 murine Myc-induced lymphoma xenografts |
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Khandekar, D.; Tiriveedhi, V. Role of BET Inhibitors in Triple Negative Breast Cancers. Cancers 2020, 12, 784. https://doi.org/10.3390/cancers12040784
Khandekar D, Tiriveedhi V. Role of BET Inhibitors in Triple Negative Breast Cancers. Cancers. 2020; 12(4):784. https://doi.org/10.3390/cancers12040784
Chicago/Turabian StyleKhandekar, Durga, and Venkataswarup Tiriveedhi. 2020. "Role of BET Inhibitors in Triple Negative Breast Cancers" Cancers 12, no. 4: 784. https://doi.org/10.3390/cancers12040784
APA StyleKhandekar, D., & Tiriveedhi, V. (2020). Role of BET Inhibitors in Triple Negative Breast Cancers. Cancers, 12(4), 784. https://doi.org/10.3390/cancers12040784