Engineering the Tumor Microenvironment in Pancreatic Cancer via Genome Editing

Pancreatic cancer remains one of the most lethal malignancies worldwide, largely due to its aggressive nature and the formidable barriers imposed by its unique tumor microenvironment (TME). The TME in pancreatic cancer consists of a complex and dynamic network of cancer-associated fibroblasts, immune cells, endothelial cells, the extracellular matrix, and a host of signaling molecules. This intricate ecosystem not only facilitates tumor progression and metastasis but also contributes to profound resistance to conventional therapies, including chemotherapy, radiotherapy, and immunotherapy.Advances in genome editing—most notably the CRISPR/Cas system, base editors, and prime editors—are opening up new avenues for understanding and manipulating the TME at a molecular and cellular level. These breakthroughs provide powerful tools for precise genetic modification of the diverse cell types and signaling pathways within the pancreatic cancer microenvironment. By enabling direct reprogramming or functional knockout of genes within TME components, genome editing holds promise for enhancing the immune response against tumors, disrupting pathological stromal-tumor interactions, and improving the efficacy of existing and emerging therapies.This Research Topic aims to highlight cutting-edge research and reviews that leverage genome editing technologies to investigate or therapeutically target the TME in pancreatic cancer. We invite submissions that address, but are not limited to:Genetic modification of stromal and immune cells within the TME to enhance their anti-tumor properties or mitigate their tumor-promoting roles.Targeted editing of extracellular matrix proteins, cytokines, or chemokines to remodel the TME, improving therapeutic delivery and efficacy.Development and application of in vivo and ex vivo models, such as genetically engineered organoids and xenografts, for studying TME dynamics and validating novel therapeutic targets.Single-cell and multi-omics approaches to map cellular heterogeneity and genomic alterations within the TME post-editing.Examples of overcoming immune evasion, fibrosis, or therapeutic resistance through precise genome engineering.Discussion of ethical, biosafety, and translational considerations for applying genome-edited therapeutics in clinical settings.By curating this collection, we seek to foster interdisciplinary collaboration and accelerate the translation of genome editing strategies into innovative therapies that reprogram the pancreatic cancer microenvironment. Our ultimate aim is to inspire new ideas and approaches that will contribute to improved outcomes for patients affected by this challenging disease. Topic editors: Suzann Duan, Shambojit Roy Source: https://www.frontiersin.org/research-topics/73163/engineering-the-tumor-microenvironment-in-pancreatic-cancer-via-genome-editing