Molecular Regulation of Metastatic Cancer: Signaling, Immune Checkpoints, and RNA Processing

Metastasis is the leading cause of cancer-related mortality and is driven by complex interactions between tumor-intrinsic pathways and the tumor microenvironment. Tumor cells acquire the ability to invade, survive in circulation, colonize distant organs, and evade immune surveillance through dynamic molecular and cellular adaptations. Key regulators of these processes include oncogenic signaling pathways, immune checkpoint mechanisms, and post-transcriptional modifications such as RNA processing.Immune checkpoints including PD-1/PD-L1, CTLA-4, and other emerging regulators, play a critical role in suppressing antitumor immunity in metastatic contexts. At the same time, aberrant signaling through pathways such as MAPK, PI3K/AKT, JAK/STAT, and MYC-driven networks not only drives proliferation and invasion but also interacts with immune regulation and RNA processing to shape tumor plasticity and therapy resistance. Post-transcriptional mechanisms, including alternative splicing and RNA-binding protein activity, further contribute to tumor heterogeneity and adaptive responses that support metastasis and immune escape.This Research Topic provides a platform for studies that examine the molecular regulation of metastatic cancer at the intersection of signaling pathways, immune checkpoint control, and RNA processing. We welcome original research, reviews, and perspectives that address mechanistic insights, preclinical models, biomarker discovery, and translational strategies. The goal is to integrate diverse molecular perspectives to advance our understanding of metastatic progression and identify actionable targets for therapeutic intervention.We welcome manuscripts related to (but are not limited to):• Dysregulated signaling pathways driving metastatic progression and therapy resistance• Immune checkpoint regulation and tumor immune evasion• Crosstalk between oncogenic signaling and immune pathways• RNA processing and post-transcriptional regulation contributing to metastasis• Mechanisms of resistance to targeted therapies or immunotherapies• Tumor–immune microenvironment interactions at metastatic sites• Integrative therapeutic strategies combining signaling modulation, checkpoint inhibition, and RNA-targeted approaches• Predictive biomarkers for metastasis and therapy response• Epigenetic regulation of oncogenic and immune-related signaling pathways• Hypoxia-driven signaling networks influencing immune escape and drug resistanceThis Research Topic aims to explore how signaling pathways, immune checkpoint regulation, and RNA processing collectively drive metastatic cancer and identify novel therapeutic opportunitiesThis Research Topic will consider original research, reviews, systematic reviews, methods, perspectives, opinions, and case reports. Topic editors: Madan Kumar Arumugam, Soumya Iyer Source: https://www.frontiersin.org/research-topics/77105/molecular-regulation-of-metastatic-cancer-signaling-immune-checkpoints-and-rna-processing