Colorectal cancer(CRC)remains one of the most common malignancies in the world.Although surgical resection combined with adjuvant therapy is effective at the early stages of the disease,resistance to conventional ther...Colorectal cancer(CRC)remains one of the most common malignancies in the world.Although surgical resection combined with adjuvant therapy is effective at the early stages of the disease,resistance to conventional therapies is frequently observed in advanced stages,where treatments become ineffective.Resistance to cisplatin,irinotecan and 5-fluorouracil chemotherapy has been shown to involve mitogen-activated protein kinase(MAPK)signaling and recent studies identified p38αMAPK as a mediator of resistance to various agents in CRC patients.Studies published in the last decade showed a dual role for the p38αpathway in mammals.Its role as a negative regulator of proliferation has been reported in both normal(including cardiomyocytes,hepatocytes,fibroblasts,hematopoietic and lung cells)and cancer cells(colon,prostate,breast,lung tumor cells).This function is mediated by the negative regulation of cell cycle progression and the transduction of some apoptotic stimuli.However,despite its anti-proliferative and tumor suppressor activity in some tissues,the p38αpathway may also acquire an oncogenic role involving cancer related-processes such as cell metabolism,invasion,inflammation and angiogenesis.In this review,we summarize current knowledge about the predominant role of the p38αMAPK pathway in CRC development and chemoresistance.In our view,this might help establish the therapeutic potential of the targeted manipulation of this pathway in clinical settings.展开更多
Familial adenomatous polyposis(FAP)and MUTYH-associ-ated polyposis(MAP)are colon cancer predisposition syn-dromes.FAP is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polypo...Familial adenomatous polyposis(FAP)and MUTYH-associ-ated polyposis(MAP)are colon cancer predisposition syn-dromes.FAP is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polyposis coli(APC)gene and characterized by hundreds to thousands of colorectal adenomas.展开更多
Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and gastrointestinal(GI)hamartomatous polyposis and is associated with an increased risk of gastrointestinal...Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and gastrointestinal(GI)hamartomatous polyposis and is associated with an increased risk of gastrointestinal,breast,gynecologic and other extra-GI malignancies.The serine/threonine kinase 11(STK11)gene has been identi-fied as a pathogenic factor in PJS.STK11 is a tumor sup-pressor gene located on chromosome 19p13.3 and includes 9 coding exons.1 The STK11 protein is composed of 433 amino acids(aa)and comprises a kinase catalytic region(aa 49e309)as well as N-and C-terminal regulatory domains.展开更多
基金Supported by Italian Association for Cancer Research(AIRC)fellowship(to Grossi V)Italian Foundation for Cancer Research(FIRC)fellowships(to Peserico A and Tezil T)+1 种基金Investigator Grant 2010 No.IG10177 to Simone C from the Italian Association for Cancer Research(AIRC)FIRB"Futuro in Ricerca"RBFR12VP3Q_003(to Simone C)from the Italian MIUR
文摘Colorectal cancer(CRC)remains one of the most common malignancies in the world.Although surgical resection combined with adjuvant therapy is effective at the early stages of the disease,resistance to conventional therapies is frequently observed in advanced stages,where treatments become ineffective.Resistance to cisplatin,irinotecan and 5-fluorouracil chemotherapy has been shown to involve mitogen-activated protein kinase(MAPK)signaling and recent studies identified p38αMAPK as a mediator of resistance to various agents in CRC patients.Studies published in the last decade showed a dual role for the p38αpathway in mammals.Its role as a negative regulator of proliferation has been reported in both normal(including cardiomyocytes,hepatocytes,fibroblasts,hematopoietic and lung cells)and cancer cells(colon,prostate,breast,lung tumor cells).This function is mediated by the negative regulation of cell cycle progression and the transduction of some apoptotic stimuli.However,despite its anti-proliferative and tumor suppressor activity in some tissues,the p38αpathway may also acquire an oncogenic role involving cancer related-processes such as cell metabolism,invasion,inflammation and angiogenesis.In this review,we summarize current knowledge about the predominant role of the p38αMAPK pathway in CRC development and chemoresistance.In our view,this might help establish the therapeutic potential of the targeted manipulation of this pathway in clinical settings.
基金funded by the research funding program“Ricerca Corrente 2019e2021,2021-2023”to Cristiano Simone,“Ricerca Corrente 2022-2024”to Vittoria Disciglio,“Ricerca Corrente 2022-2024”to Candida Fasano,AIRC fellowship for Italy“ID.26678-2021”to Martina Lepore Signorile,“Starting Grant”SG-2019-12371540 to Paola Sanese from the Italian Ministry of Health and the 2017 PRIN(Research Projects of National Relevance)n.2017WNKSLr-LS4 from the Italian MIUR to Cristiano Simone.
文摘Familial adenomatous polyposis(FAP)and MUTYH-associ-ated polyposis(MAP)are colon cancer predisposition syn-dromes.FAP is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polyposis coli(APC)gene and characterized by hundreds to thousands of colorectal adenomas.
基金This work was supported by the Italian Association for Cancer Research(IG grant N.23794 to C.S.),by the Italian Ministry of Health“Ricerca Corrente 2018e20202019e2021”to C.S.,and by the Italian Ministry of Education,University and Research(MIUR)“PRIN-Research Projects of National Relevance”(PRIN 2017,N.2017WNKSLRLS4)to C.
文摘Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and gastrointestinal(GI)hamartomatous polyposis and is associated with an increased risk of gastrointestinal,breast,gynecologic and other extra-GI malignancies.The serine/threonine kinase 11(STK11)gene has been identi-fied as a pathogenic factor in PJS.STK11 is a tumor sup-pressor gene located on chromosome 19p13.3 and includes 9 coding exons.1 The STK11 protein is composed of 433 amino acids(aa)and comprises a kinase catalytic region(aa 49e309)as well as N-and C-terminal regulatory domains.