PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32024199-0 2020 Regorafenib Alteration of the BCL-xL/MCL-1 Ratio Provides a Therapeutic Opportunity for BH3-Mimetics in Hepatocellular Carcinoma Models. regorafenib 0-11 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 37-42 32724460-0 2020 Mcl-1 inhibition overcomes intrinsic and acquired regorafenib resistance in colorectal cancer. regorafenib 50-61 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 0-5 32724460-2 2020 We previously showed that resistance to regorafenib, a multi-kinase inhibitor for treating colorectal cancer (CRC) patients, can be caused by mutations in the tumor suppressor FBW7, which block degradation of the pro-survival Bcl-2 family protein Mcl-1. regorafenib 40-51 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 247-252 32724460-3 2020 We tested if Mcl-1 inhibition can be used to develop a precision combination therapy for overcoming regorafenib resistance. regorafenib 100-111 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 13-18 32724460-7 2020 RESULTS: We found that highly potent and specific Mcl-1 inhibitors such as S63845 overcame regorafenib resistance by restoring apoptosis in multiple regorafenib-resistant CRC models. regorafenib 91-102 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 50-55 32724460-7 2020 RESULTS: We found that highly potent and specific Mcl-1 inhibitors such as S63845 overcame regorafenib resistance by restoring apoptosis in multiple regorafenib-resistant CRC models. regorafenib 149-160 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 50-55 32724460-8 2020 Mcl-1 inhibition re-sensitized CRC tumors with intrinsic and acquired regorafenib resistance in vitro and in vivo, including those with FBW7 mutations. regorafenib 70-81 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 0-5 32724460-9 2020 Importantly, Mcl-1 inhibition also sensitized FBW7-mutant PDO and PDX models to regorafenib. regorafenib 80-91 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 13-18 32724460-11 2020 CONCLUSIONS: Our results demonstrate that Mcl-1 inhibitors can overcome intrinsic and acquired regorafenib resistance in CRCs by restoring apoptotic response. regorafenib 95-106 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 42-47 32024199-7 2020 Moreover, regorafenib-resistant HepG2 cells displayed increased BCL-xL and reduced MCL-1 expression, while A-1331852 reinstated regorafenib efficacy in vitro and in a xenograft mouse model. regorafenib 10-21 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 83-88 32024199-9 2020 CONCLUSION: Regorafenib primes tumor cells to BH3-mimetic-induced cell death, allowing BCL-xL inhibition with A-1331852 or other strategies based on BCL-xL degradation to enhance regorafenib efficacy, offering a novel approach for HCC treatment, particularly for tumors with an elevated BCL-xL/MCL-1 ratio. regorafenib 12-23 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 294-299 31349793-0 2019 Inhibition of cyclin E1 sensitizes hepatocellular carcinoma cells to regorafenib by mcl-1 suppression. regorafenib 69-80 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 84-89 31238539-8 2019 After regorafenib treatment, downregulation of related genes in invasion (vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9)), proliferation (CyclinD1) and anti-apoptosis (X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia-1 (MCL-1), and cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (C-FLIP)) were found. regorafenib 6-17 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 249-272 31238539-8 2019 After regorafenib treatment, downregulation of related genes in invasion (vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9)), proliferation (CyclinD1) and anti-apoptosis (X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia-1 (MCL-1), and cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (C-FLIP)) were found. regorafenib 6-17 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 274-279 33922992-5 2021 In addition, the inhibition of MCL-1 by siRNA combined with regorafenib allowed for a significantly greater inhibition of cell growth, compared to regorafenib alone. regorafenib 147-158 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 31-36 29682179-8 2018 Moreover, regorafenib administration also modified the BCL-2/MCL-1 ratio and navitoclax sensitized hepatoma cells to regorafenib by a mitochondrial caspase-dependent mechanism. regorafenib 10-21 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 61-66 27399335-8 2017 CRC cells selected for regorafenib resistance have progressive enrichment of pre-existing FBW7 hotspot mutations, and are cross-resistant to other targeted drugs that induce Mcl-1 degradation. regorafenib 23-34 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 174-179 27399335-9 2017 Furthermore, a selective Mcl-1 inhibitor restores regorafenib sensitivity in CRC cells with intrinsic or acquired resistance. regorafenib 50-61 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 25-30 26561209-11 2015 Regorafenib suppressed Mcl-1 and Bcl-XL in treated cancer cells that may have contributed to the anticancer efficacy including in combination with 5-FU. regorafenib 0-11 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 23-28 33922992-9 2021 Taken together, magnolol sensitized HCC to regorafenib, which was correlated with the reduction of VEGF-A and MCL-1 and the induction of apoptosis. regorafenib 43-54 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 110-115