Deciphering Genomic Aberrations and Microenvironmental Crosstalk in Refractory Tumors for Novel Therapeutic Targets

Background: Refractory tumors, such as pancreatic ductal adenocarcinoma, glioblastoma, advanced urothelial carcinoma, castration-resistant prostate cancer, and triple-negative breast cancer, represent the most challenging frontiers in oncology. These malignancies are characterized by rapid progression and intrinsic resistance to conventional therapies. The failure of standard treatments is often attributed to a complex interplay between tumor-intrinsic genomic aberrations and an immunosuppressive tumor microenvironment (TME). While genetic mutations drive malignant proliferation, the surrounding stroma and immune cells create a physical and biological barrier that limits drug delivery and efficacy. Understanding the specific molecular mechanisms governing these interactions is urgent for breaking the bottleneck of current treatment failures.

Goal: The primary goal of this Research Topic is to identify actionable therapeutic targets by analyzing the relationship between genomic features and microenvironmental characteristics. We aim to gather research that dissects how specific genetic alterations reprogram the TME to favor immune evasion and metastasis. We explicitly encourage studies that utilize high-throughput data to screen for potential biomarkers and therapeutic vulnerabilities. By integrating genomic and transcriptomic data, this collection seeks to pinpoint key molecules that can be targeted to sensitize refractory tumors to immunotherapy or targeted agents. The ultimate objective is to translate these molecular findings into more precise clinical intervention strategies.

Scope and Information for Authors: We welcome Original Research, Reviews, and Methods articles. Both computational and experimental approaches are highly encouraged. Potential themes include:
• Computational identification of robust genomic and transcriptomic signatures that specifically predict patient prognosis and therapeutic response in refractory tumors.
• Mechanisms of crosstalk between tumor cells and the immune microenvironment driven by specific genetic mutations.
• Elucidation of molecular mechanisms driving resistance to chemotherapy, immunotherapy, or targeted therapy, with a focus on identifying novel targets to restore therapeutic sensitivity.
• Integrated analysis of metabolic reprogramming or hypoxic signatures and their role in reshaping the immunosuppressive tumor microenvironment (TME).
• Spatial analysis of the TME to visualize drug resistance niches (optional but encouraged).
Manuscripts consisting of bioinformatics, computational analyses of public data should be accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo) or are highly innovative.