BET proteins,which influence gene expression and contribute to the development of cancer,are epigenetic interpreters.Thus,BET inhibitors represent a novel form of epigenetic anticancer treatment.Although preliminary c...BET proteins,which influence gene expression and contribute to the development of cancer,are epigenetic interpreters.Thus,BET inhibitors represent a novel form of epigenetic anticancer treatment.Although preliminary clinical trials have shown the anticancer potential of BET inhibitors,it appears that these drugs have limited effectiveness when used alone.Therefore,given the limited monotherapeutic activity of BET inhibitors,their use in combination with other drugs warrants attention,including the meaningful variations in pharmacodynamic activity among chosen drug combinations.In this paper,we review the function of BET proteins,the preclinical justification for BET protein targeting in cancer,recent advances in small-molecule BET inhibitors,and preliminary clinical trial findings.We elucidate BET inhibitor resistance mechanisms,shed light on the associated adverse events,investigate the potential of combining these inhibitors with diverse therapeutic agents,present a comprehensive compilation of synergistic treatments involving BET inhibitors,and provide an outlook on their future prospects as potent antitumor agents.We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.展开更多
A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor kil...A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.展开更多
Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer,its effectiveness in patients without BRCA mutations...Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer,its effectiveness in patients without BRCA mutations remains poorly investigated.This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context.Using real-world data from 11 high-volume tertiary care centers in China,a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer.The primary objective was 1-year progression-free survival rate.Safety was also evaluated.Fifty patients with a median age of 54 years were included,and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency(HRD).The 1-year PFS rate was 75.2%(95%CI,63.4 to 89.2),and the median PFS was 21.0 months(95%CI,13.8 to 28.2).All the patients received olaparib at a starting dose of 300 mg twice daily,and none experienced serious adverse events(AEs).Eight(16%)patients had dose adjustment,but none discontinued olaparib treatment due to AEs.We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.展开更多
基金supported by the National Natural Science Foundation of China(nos.81872507 and 82173238)the Heilongjiang Provincial Natural Science Foundation Key Projects(ZD2020H007)+4 种基金the Harbin Medical University Cancer Hospital(CN)Nn10 Project(Nn10py2017-01)the China Postdoctoral Science Foundation(296266)the Heilongjiang Province Doctoral Post-doctoral Fund(LBH-Z21177)the Fundamental Research Funds for the Provincial Universities(2022-KYYWF-0291)the Harbin Medical University Haiyan Youth Fund(JJQN2022-3).
文摘BET proteins,which influence gene expression and contribute to the development of cancer,are epigenetic interpreters.Thus,BET inhibitors represent a novel form of epigenetic anticancer treatment.Although preliminary clinical trials have shown the anticancer potential of BET inhibitors,it appears that these drugs have limited effectiveness when used alone.Therefore,given the limited monotherapeutic activity of BET inhibitors,their use in combination with other drugs warrants attention,including the meaningful variations in pharmacodynamic activity among chosen drug combinations.In this paper,we review the function of BET proteins,the preclinical justification for BET protein targeting in cancer,recent advances in small-molecule BET inhibitors,and preliminary clinical trial findings.We elucidate BET inhibitor resistance mechanisms,shed light on the associated adverse events,investigate the potential of combining these inhibitors with diverse therapeutic agents,present a comprehensive compilation of synergistic treatments involving BET inhibitors,and provide an outlook on their future prospects as potent antitumor agents.We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.
基金the Harbin Medical University Cancer Hospital(CN)Nn10 Project(Nn10py2017-01)。
文摘A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.
文摘Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer,its effectiveness in patients without BRCA mutations remains poorly investigated.This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context.Using real-world data from 11 high-volume tertiary care centers in China,a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer.The primary objective was 1-year progression-free survival rate.Safety was also evaluated.Fifty patients with a median age of 54 years were included,and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency(HRD).The 1-year PFS rate was 75.2%(95%CI,63.4 to 89.2),and the median PFS was 21.0 months(95%CI,13.8 to 28.2).All the patients received olaparib at a starting dose of 300 mg twice daily,and none experienced serious adverse events(AEs).Eight(16%)patients had dose adjustment,but none discontinued olaparib treatment due to AEs.We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
