Prostate cancer is one of the most common diseases in men worldwide.Surgery,radiation therapy,and hormonal therapy are effective treatments for early-stage prostate cancer.However,the development of castration-resista...Prostate cancer is one of the most common diseases in men worldwide.Surgery,radiation therapy,and hormonal therapy are effective treatments for early-stage prostate cancer.However,the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer.To develop novel drugs for castration-resistant prostate cancer,the molecular mechanisms of prostate cancer progression must be elucidated.Among the signaling pathways regulating prostate cancer development,recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family(WNT)signaling pathways,mainly that involving WNT5A,in prostate cancer progression and metastasis;however,its role remains controversial.Moreover,chromatin remodelers such as the switch/sucrose nonfermentable(SWI/SNF)complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes.Here,we review the roles of noncanonical WNT signaling pathways,chromatin remodelers,and epigenetic enzymes in the development and progression of prostate cancer.展开更多
The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer tr...The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.展开更多
基金This review was supported by Grant-in-Aid for Scientific Research([C]grant No.22K09442).
文摘Prostate cancer is one of the most common diseases in men worldwide.Surgery,radiation therapy,and hormonal therapy are effective treatments for early-stage prostate cancer.However,the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer.To develop novel drugs for castration-resistant prostate cancer,the molecular mechanisms of prostate cancer progression must be elucidated.Among the signaling pathways regulating prostate cancer development,recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family(WNT)signaling pathways,mainly that involving WNT5A,in prostate cancer progression and metastasis;however,its role remains controversial.Moreover,chromatin remodelers such as the switch/sucrose nonfermentable(SWI/SNF)complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes.Here,we review the roles of noncanonical WNT signaling pathways,chromatin remodelers,and epigenetic enzymes in the development and progression of prostate cancer.
基金Supported by"Institut National de la Sante et de la Recherche Médicale"(Inserm)"Centre National de la Recherche Scientifique"(CNRS)"la Ligue Nationale contre le Cancer"(Committees 59,60 and 62)
文摘The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.
