Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,pro...Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.展开更多
Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular space.They exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and p...Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular space.They exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological conditions.Human serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses challenges.These vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease biomarkers.Especially in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic biomarkers.Moreover,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical significance.The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled.Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future.In this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.展开更多
Colorectal cancer(CRC)is a predominant life-threatening cancer,with liver and peritoneal metastases as the primary causes of death.Intestinal inflammation,a known CRC risk factor,nurtures a local inflammatory environm...Colorectal cancer(CRC)is a predominant life-threatening cancer,with liver and peritoneal metastases as the primary causes of death.Intestinal inflammation,a known CRC risk factor,nurtures a local inflammatory environment enriched with tumor cells,endothelial cells,immune cells,cancer-associated fibroblasts,immunosuppressive cells,and secretory growth factors.The complex interactions of aberrantly expressed cytokines,chemokines,growth factors,and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes.Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment,which is partly achieved by the recruitment of immunosuppressive cells.These cells impart features such as cancer stem cell-like properties,drug resistance,invasion,and formation of the premetastatic niche in distant organs,promoting metastasis and aggressive CRC growth.A deeper understanding of the cytokineand chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC.Here,we summarized the current knowledge of cytokine-and chemokine-mediated crosstalk in the inflammatory tumor microenvironment,which drives immunosuppression,resistance to therapeutics,and metastasis during CRC progression.We also outlined the potential of this crosstalk as a novel therapeutic target for CRC.The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.展开更多
Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-020-00419-w,published online 12 January 2021 After online publication of the article1,the authors noticed an error in affiliation o...Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-020-00419-w,published online 12 January 2021 After online publication of the article1,the authors noticed an error in affiliation of co-authors Dr.Nissar A.Wani.Dr.Wani is erroneously linked to Sidra Medicine,Doha,Qatar who is actually working at the Department of Biotechnology,School of Life Sciences,Central University of Kashmir,Ganderbal,Jammu&Kashmir,India.Also,the department name"Cancer Research Department"for the first author Ajaz A.Bhat is missing.展开更多
Head and neck squamous cell carcinoma(HNSCC)is a very aggressive disease with a poor prognosis for advanced-stage tumors.Recent clinical,genomic,and cellular studies have revealed the highly heterogeneous and immunosu...Head and neck squamous cell carcinoma(HNSCC)is a very aggressive disease with a poor prognosis for advanced-stage tumors.Recent clinical,genomic,and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC.Despite signifcant advances in multimodal therapeutic interventions,failure to cure and recurrence are common and account for most deaths.It is becoming increasingly apparent that tumor microenvironment(TME)plays a critical role in HNSCC tumorigenesis,promotes the evolution of aggressive tumors and resistance to therapy,and thereby adversely affects the prognosis.A complete understanding of the TME factors,together with the highly complex tumor-stromal interactions,can lead to new therapeutic interventions in HNSCC.Interestingly,different molecular and immune landscapes between HPV^(+ve) and HPV^(-ve)(human papillomavirus)HNSCC tumors offer new opportunities for developing individualized,targeted chemoimmunotherapy(CIT)regimen.This review highlights the current understanding of the complexity between HPV^(+ve) and HPV^(-ve) HNSCC TME and various tumor-stromal cross-talk modulating processes,including epithelial-mesenchymal transition(EMT),anoikis resistance,angiogenesis,immune surveillance,metastatic niche,therapeutic resistance,and development of an aggressive tumor phenotype.Furthermore,we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV^(+ve) and HPV^(-ve) HNSCC.展开更多
基金supported by Sidra Medicine Research Fund to Ajaz A.Bhat(grant number:SDR400190)Ammira S.Al-Shabeeb Akil(grant number:SDR400175).
文摘Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.
基金Sidra Medicine Research Fund funded this study to A.A.B.[SDR400105]and A.S.A.S.A.[SDR400175]Ramalingaswami Fellowship(Grant number:D.O.NO.BT/HRD/35/02/2006)from the Department of Biotechnology,&Core Research Grant(CRG/2021/003805)from Science and Engineering Research Board,Govt.of India,New Delhi to M.A.M.Promotion of University Research and Scientific Excellence(PURSE)(SR/PURSE/2022/121)grant from the Department of Science and Technology,Govt.of India,New Delhi,to the Islamic University of Science and Technology(IUST),Awantipora.Open Access funding provided by the Qatar National Library。
文摘Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular space.They exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological conditions.Human serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses challenges.These vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease biomarkers.Especially in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic biomarkers.Moreover,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical significance.The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled.Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future.In this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.
基金Ramalingaswami Fellowship,Grant/Award Number:D.O.NO.BT/HRD/35/02/2006the Department of Biotechnology,&Core Research grant,Grant/Award Number:CRG/2021/003805+1 种基金Science and Engineering Research Board(SERB),Govt.of India,New DelhiSidra Medicine Precision Program,Grant/Award Numbers:5081012003,5081012002。
文摘Colorectal cancer(CRC)is a predominant life-threatening cancer,with liver and peritoneal metastases as the primary causes of death.Intestinal inflammation,a known CRC risk factor,nurtures a local inflammatory environment enriched with tumor cells,endothelial cells,immune cells,cancer-associated fibroblasts,immunosuppressive cells,and secretory growth factors.The complex interactions of aberrantly expressed cytokines,chemokines,growth factors,and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes.Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment,which is partly achieved by the recruitment of immunosuppressive cells.These cells impart features such as cancer stem cell-like properties,drug resistance,invasion,and formation of the premetastatic niche in distant organs,promoting metastasis and aggressive CRC growth.A deeper understanding of the cytokineand chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC.Here,we summarized the current knowledge of cytokine-and chemokine-mediated crosstalk in the inflammatory tumor microenvironment,which drives immunosuppression,resistance to therapeutics,and metastasis during CRC progression.We also outlined the potential of this crosstalk as a novel therapeutic target for CRC.The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.
文摘Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-020-00419-w,published online 12 January 2021 After online publication of the article1,the authors noticed an error in affiliation of co-authors Dr.Nissar A.Wani.Dr.Wani is erroneously linked to Sidra Medicine,Doha,Qatar who is actually working at the Department of Biotechnology,School of Life Sciences,Central University of Kashmir,Ganderbal,Jammu&Kashmir,India.Also,the department name"Cancer Research Department"for the first author Ajaz A.Bhat is missing.
基金This study was supported by Ramalingaswami Fellowship(Grant number:D.O.NO.BT/HRD/35/02/2006)from the Department of Biotechnology,Government of India,New Delhi to Muzafar A.MachaMohammad Haris is funded by a grant(5071012001)from Sidra Medicine Doha,QatarAjaz A.Bhat is supported by Sidra Medicine internal grant(5011041002).We thank Dr.Vineeta Tanwar(Ohio State University,Columbus,Ohio,USA)for her professional assistance in editing the paper.
文摘Head and neck squamous cell carcinoma(HNSCC)is a very aggressive disease with a poor prognosis for advanced-stage tumors.Recent clinical,genomic,and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC.Despite signifcant advances in multimodal therapeutic interventions,failure to cure and recurrence are common and account for most deaths.It is becoming increasingly apparent that tumor microenvironment(TME)plays a critical role in HNSCC tumorigenesis,promotes the evolution of aggressive tumors and resistance to therapy,and thereby adversely affects the prognosis.A complete understanding of the TME factors,together with the highly complex tumor-stromal interactions,can lead to new therapeutic interventions in HNSCC.Interestingly,different molecular and immune landscapes between HPV^(+ve) and HPV^(-ve)(human papillomavirus)HNSCC tumors offer new opportunities for developing individualized,targeted chemoimmunotherapy(CIT)regimen.This review highlights the current understanding of the complexity between HPV^(+ve) and HPV^(-ve) HNSCC TME and various tumor-stromal cross-talk modulating processes,including epithelial-mesenchymal transition(EMT),anoikis resistance,angiogenesis,immune surveillance,metastatic niche,therapeutic resistance,and development of an aggressive tumor phenotype.Furthermore,we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV^(+ve) and HPV^(-ve) HNSCC.
