Copyright ©The Author(s) 2022.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 75-89
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.75
Table 1 Preclinical models of Bromodomain and extra-terminal inhibitors in gastrointestinal cancers
GI cancers models
BET inhibitors
Combination with
JQ-1Bortezomib MYC, FOXM1G2/M arrest[47]
JQ-1-HGF, METCancer-associated fibroblasts[98]
Apabetalone-APOA1 Intracellular cholesterol metabolism[99]
JQ-1BEZ235 (PI3K/mTOR inhibitor)RTKsOvercome resistance to PI3K/mTOR inhibition[40]
JQ-1Sulforaphane (HDAC3 inhibitor)ERCC2Nucleotide excision repair pathway[48]
I-BET151, bromosporine-BRD4, SNAIL, SLUG EMT [100]
SMAD4-defificient CRCOTX-015-MYCMYC-p21 axis, G1 cell cycle arrest[54]
Colon cancerJQ-1-Nkd2, β-catenin, miR-21 Wnt/β-catenin signaling, apoptosis[45]
Gastric and colon cancerJQ-1Arsenic sulfideNFATs, c-MYCMitochondrial pathway induced cell apoptosis[51]
PDACJQ-1-HMGA2Block growth of chemoresistant cells[55]
JQ-1Olaparib (PARP inhibitor)BRD2/4, Ku80, RAD51DNA damage[60]
JQ-1SAHA (HDAC inhibitor)p57Cell death[61]
JQ-1GemcitabineHMGCS2, APOC1DNA damage and apoptosis[62]
CPI203-MYC, GLI, SHHSHH-GLI signaling pathway, cell cycle progression[24]
Pancreatic cancerJQ-1, OTX-015Quercetin BRD4(JQ-1) and hnRNPA1(Quercetin)Apoptosis[63]
KDM6A null pancreatic cancerJQ-1-MYC, p63, RUNX3Reverse squamous differentiation[101,102]
Liver cancer JQ-1-BRD4, E2F2BRD4-E2F2-cell cycle regulation axis, [34]
JQ-1-PD-L1, PD-L2 PD-1/PD-L1 signaling[71]
HCCJQ-1, I-BET762Anti-PD-L1 AbBRD4, C/EBPβ, p300Suppress M-MDSCs, enhance PD-L1 blockade efficacy[73]
JQ-1-MYCImpair mitochondrial respiration and glycolysis, induce apoptosis[66]
Hjp-6-171GSK3β inhibitor (CHIR-98014)β-catenin, NOTUMWNT pathway[68]
SF1126 (Pan PI3K/BRD4 Inhibitor)SorafenibBRD4, c-MYCRas/Raf/MAPK, PI3K/AKT/mTOR pathways[90]
JQ-1-PES1 Cell proliferation, glycolysis[35]
JQ-1FlavopiridolMcl-1 Apoptosis[67]
JQ-1, OTX-015-SMARCA4Down-regulate migration related genes[65]
CCA2 JQ-1PI3K/mTOR inhibitorsc-Myc, YAPOvercome resistance to PI3K/mTOR inhibition[64]
Gastric cancerJQ-1-BRD4, E2FE2F/miR-106b-5p/p21 axis, cellular senescence[32]
JQ-1-RUNX2 RUNX2/NID1 signaling, site-specific chromatinremodeling[75]
JQ1, PNZ5 -c-MYCApoptosis[33,74]
iBET-151PaclitaxelRTKG1 cell cycle arrest[79]
AZD5153-Sirt5, Mus81 Sirt5/Mus81/ZEB1 axis, inhibit metastasis[76]
GACJQ-1CA3 (YAP inhibitor)c-MYCGal3/RalA/YAP1/c-MYC axis[78]
Table 2 Clinical trials of Bromodomain and extra-terminal inhibitors in gastrointestinal cancers (Trial ID on
Combination with
Clinical phase
Trial ID
INCB054329 -Solid Tumors and Hematologic Malignancy (CRPC, BC, HGSC, CRC, Ewing sarcoma, Pancreatic adenocarcinoma, AML, MDS, MF, MM)Terminated due to PK variabilityPhase I/IINCT02431260
INCB057643Gemcitabine; Paclitaxel; Rucaparib; Abiraterone; Ruxolitinib; AzacitidineSolid Tumors (CRPC, BC, HGSC, CRC, Glioblastoma multiforme, Ewing sarcoma, Pancreatic adenocarcinoma, AML, MDS)Terminated due to safety issuesPhase I/IINCT02711137
AZD5153OlaparibMalignant Solid Tumors, Lymphoma, Ovarian Cancer, Breast Cancer, Pancreatic Cancer, Prostate CancerActive, not recruiting Phase INCT03205176
I-BET762 (Molibresib, GSK525762)EntinostatSolid tumors (Advanced Malignant Solid Neoplasm, Refractory Malignant Solid Neoplasm, Refractory Pancreatic Carcinoma, Stage II/IIA/IIB/III/IV Pancreatic cancer AJCC v8, Unresectable Pancreatic Carcinoma) or LymphomasWithdrawn (Other-Protocol moved to Disapprove) Phase INCT03925428
SF1126-Advanced Hepatocellular CarcinomaActive, not recruiting Phase INCT03059147