Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer ...Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.展开更多
Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic re...Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.展开更多
Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while add...Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.展开更多
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020,accessed on 01 July 2025)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020,accessed on 01 July 2025).Institutional.
文摘Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020).
文摘Background:The Colorectal Cancer(CRC)pathogenesis and therapeutic efficacy are influenced by the gut microbiome,making it a promising biomarker for predicting treatment responses and adverse effects.This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.Methods:Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025,respectively.Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes.RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies,respectively.Data extracted was narratively analyzed.Results:Six studies involving a total of 361 individuals were included.Therapeutic interventions,either standard treatments and/or those targeting the gut microbiome,generally increased probiotic taxa and reduced pro-carcinogenic bacteria.However,no consistent pattern of improved clinical outcomes was observed,suggesting that treatment mechanisms,the tumor’s nature,and individual characteristics play critical roles in microbiome modulation.Conclusion:The gut microbiome holds significant potential in clinical settings.Nonetheless,further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms,the tumor’s nature,and individual characteristics as modulators,in order to optimize clinical outcomes.
文摘Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
