Beyond the Gut:The intratumoral microbiome’s influence on tumorigenesis and treatment response

The intratumoral microbiome(TM)refers to the microorganisms in the tumor tissues,including bacteria,fungi,viruses,and so on,and is distinct from the gut microbiome and circulating microbiota.TM is strongly associated with tumorigenesis,progression,metastasis,and response to therapy.This paper highlights the current status of TM.Tract sources,adjacent normal tissue,circulatory system,and concomitant tumor co-metastasis are the main origin of TM.The advanced techniques in TM analysis are comprehensively summarized.Besides,TMis involved in tumor progression through several mechanisms,including DNA damage,activation of oncogenic signaling pathways(phosphoinositide 3-kinase[PI3K],signal transducer and activator of transcription[STAT],WNT/β-catenin,and extracellular regulated protein kinases[ERK]),influence of cytokines and induce inflammatory responses,and interaction with the tumor microenvironment(anti-tumor immunity,pro-tumor immunity,and microbial-derived metabolites).Moreover,promising directions of TM in tumor therapy include immunotherapy,chemotherapy,radiotherapy,the application of probiotics/prebiotics/synbiotics,fecal microbiome transplantation,engineered microbiota,phage therapy,and oncolytic virus therapy.The inherent challenges of clinical application are also summarized.This review provides a comprehensive landscape for analyzing TM,especially the TM-related mechanisms and TM-based treatment in cancer.

Patient-derived xenograft models in cancer therapy:technologies and applications

Patient-derived xenograft(PDX)models,in which tumor tissues from patients are implanted into immunocompromised or humanized mice,have shown superiority in recapitulating the characteristics of cancer,such as the spatial structure of cancer and the intratumor heterogeneity of cancer.Moreover,PDX models retain the genomic features of patients across different stages,subtypes,and diversified treatment backgrounds.Optimized PDX engraftment procedures and modern technologies such as multi-omics and deep learning have enabled a more comprehensive depiction of the PDX molecular landscape and boosted the utilization of PDX models.These irreplaceable advantages make PDX models an ideal choice in cancer treatment studies,such as preclinical trials of novel drugs,validating novel drug combinations,screening drug-sensitive patients,and exploring drug resistance mechanisms.In this review,we gave an overview of the history of PDX models and the process of PDX model establishment.Subsequently,the review presents the strengths and weaknesses of PDX models and highlights the integration of novel technologies in PDX model research.Finally,we delineated the broad application of PDX models in chemotherapy,targeted therapy,immunotherapy,and other novel therapies.