AI-driven multi-omics and organoid platforms to unravel PTEN-mediated immune escape and immunotherapy outcomes in colorectal cancer

Colorectal cancer research increasingly focuses on the molecular and immunological complexities that drive heterogeneity in clinical outcomes. Among key molecular players, PTEN (Phosphatase and Tensin Homolog) has emerged as a pivotal regulator of tumor biology, governing vital functions in cell proliferation, metabolism, and immune response modulation. Loss or mutation of PTEN is closely associated with immune escape in the colorectal tumor microenvironment, characterized by diminished T-cell infiltration and suboptimal responses to immunotherapy. Despite advances in multimodal therapies, most patients still do not sustain durable benefits from immune checkpoint inhibitors, highlighting the critical need for mechanistic insights into immune resistance pathways.Recent progress in multi-omics—including genomics, transcriptomics, proteomics, and metabolomics—has shed new light on the intricacies of PTEN-driven tumor–immune interactions. Especially notable is the integration of patient-derived organoid models, which faithfully recapitulate the in vivo tumor–immune ecosystem, and the application of AI-driven analytical pipelines to decipher complex datasets. These cutting-edge approaches have enabled the identification of novel biomarkers and predictive signatures; however, challenges remain in translating these findings into clinically actionable strategies and understanding context-specific effects of PTEN alterations.This Research Topic aims to bridge computational, molecular, and experimental insights to elucidate how PTEN status shapes immune evasion mechanisms and determines immunotherapy efficacy in colorectal cancer. By merging AI-empowered multi-omics analysis with functional validation in organoid systems, the objective is to uncover new biomarkers, therapeutic targets, and strategies to counteract immune resistance. Central questions include: what molecular cues underlie PTEN-driven immune exclusion, how can these be modeled and predicted using advanced AI techniques, and which interventions can sensitize PTEN-deficient tumors to immunotherapies? Ultimately, the goal is to inform precision oncology approaches that enhance personalized treatment and clinical outcomes for patients with PTEN-altered colorectal cancer.This Research Topic is defined by its focus on innovative methods that integrate AI, multi-omics, and organoid technologies to investigate PTEN-dependent immune processes in colorectal cancer, with an emphasis on translational impact. It welcomes contributions encompassing both computational modeling and experimental validation, providing a broad but focused platform for advances in the field.To gather further insights in this area, we welcome articles addressing, but not limited to, the following themes:• Multi-omics profiling of PTEN-deficient colorectal tumors• Artificial intelligence and machine learning platforms for biomarker and patient stratification• Mechanisms of immune evasion in the PTEN-deficient tumor microenvironment• Organoid and organoid–immune co-culture systems for mechanistic and therapeutic studies• Predictive markers and models of immunotherapy response and resistance• Application of single-cell and spatial omics technologies• Emerging therapeutic approaches targeting PTEN-related pathwaysWe encourage the submission of original research articles, reviews, mini-reviews, methods papers, and perspective articles that provide new insight or technological advances in this evolving field.Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.Please note that Dr. Meraj Khan is a co-founder of DigiBiomics. Topic editors: Meraj Khan, Dr Asgar Ali Source: https://www.frontiersin.org/research-topics/80254/ai-driven-multi-omics-and-organoid-platforms-to-unravel-pten-mediated-immune-escape-and-immunotherapy-outcomes-in-colorectal-cancer