The dynamic interplay between neoplastic cells and the host has been increasingly recognized as important players in the pathogenesis of cancer cachexia,a syndrome affecting~50-80%of cancer patients with various incid...The dynamic interplay between neoplastic cells and the host has been increasingly recognized as important players in the pathogenesis of cancer cachexia,a syndrome affecting~50-80%of cancer patients with various incidences of different types of malignancies.Despite its prevalence,a comprehensive understanding of cancer cachexia progression,with a holistic view at the cross-organismal,cellular and molecular levels,remains elusive.In this review,we undertake an in-depth exploration of the relevant target organs and their regulatory roles in cancer cachexia,with a particular focus on macroenvironmental interactions via various organismal crosstalk axes.Moreover,we highlight how systemic metabolic remodeling,a hallmark of cancer cachexia,plays essential roles in modulating the inflammatory responses of immune and stromal cells in the tumor microenvironment(TME).These cellular responses,in turn,disrupt energy metabolism in distant organs and perturb organismal homeostasis by secreting a variety of mediators that activate specific signaling pathways,thereby fostering a vicious cycle that exacerbates cancer cachexia.We comprehensively summarize these complex cellular and molecular networks that constitute reciprocally regulatory dynamics between systemic metabolic reprogramming and inflammatory cascades.Notably,targeting the multifaceted interplay of organismal metabolic remodeling and cancer-associated inflammation holds great promise for clinical translation,as illustrated by a series of innovative therapeutic strategies and ongoing clinical trials aimed at mitigating cachexia in cancer patients.展开更多
基金sponsored by grants from the National Key Research and Development Program of China(No.2023YFC3402100 Bin Wang)the National Natural Science Foundation of China(NSFC Nos.82192890 and 82192891 to Xiu-wu Bian,82203318 to Zongsheng He)+3 种基金the China Postdoctoral Science Foundation(No.2024M763883 to Xuan Zhang)the Science and Technology Innovation Key R&D Program of Chongqing(CSTB2023TIAD-STX0002 to Bin Wang)the Natural Science Foundation of Chongqing(Nos.CSTB2023NSCQ-LZX0156 to Bin Wang,CSTB2022NSCQ-MSX0880 to Zongsheng He,CSTB2024NSCQ-BSX0017 to Ke Li)funding from the JinFeng laboratory to Bin Wang.
文摘The dynamic interplay between neoplastic cells and the host has been increasingly recognized as important players in the pathogenesis of cancer cachexia,a syndrome affecting~50-80%of cancer patients with various incidences of different types of malignancies.Despite its prevalence,a comprehensive understanding of cancer cachexia progression,with a holistic view at the cross-organismal,cellular and molecular levels,remains elusive.In this review,we undertake an in-depth exploration of the relevant target organs and their regulatory roles in cancer cachexia,with a particular focus on macroenvironmental interactions via various organismal crosstalk axes.Moreover,we highlight how systemic metabolic remodeling,a hallmark of cancer cachexia,plays essential roles in modulating the inflammatory responses of immune and stromal cells in the tumor microenvironment(TME).These cellular responses,in turn,disrupt energy metabolism in distant organs and perturb organismal homeostasis by secreting a variety of mediators that activate specific signaling pathways,thereby fostering a vicious cycle that exacerbates cancer cachexia.We comprehensively summarize these complex cellular and molecular networks that constitute reciprocally regulatory dynamics between systemic metabolic reprogramming and inflammatory cascades.Notably,targeting the multifaceted interplay of organismal metabolic remodeling and cancer-associated inflammation holds great promise for clinical translation,as illustrated by a series of innovative therapeutic strategies and ongoing clinical trials aimed at mitigating cachexia in cancer patients.
