Interactions between radiotherapy resistance mechanisms and the tumor microenvironment

Area of Science:

• Oncology
• Cancer Biology
• Immunotherapy

Background:

• Radiotherapy (RT) resistance is a significant clinical hurdle in cancer management.
• The tumor microenvironment (TME) plays a critical role in mediating resistance to RT.
• Understanding TME-driven RT resistance mechanisms is crucial for developing effective therapies.

Purpose of the Study:

• To review and discuss mechanisms of RT resistance originating from the TME.
• To identify therapeutic strategies targeting the TME to overcome RT resistance.
• To highlight emerging technologies for exploring RT resistance.

Main Methods:

• A narrative review was conducted using PubMed and Web of Science databases.
• Studies focusing on the regulative network and treatments of RT resistance from TME perspectives were identified.
• Key genes, pathways, and TME-modulating factors were analyzed.

Main Results:

• RT alters the immune TME, impacting immune cell infiltration and function, which is central to RT resistance.
• Phenotypes like autophagy, senescence, oxidative stress, and angiogenesis contribute to RT resistance.
• Key pathways (e.g., TGF-β, P53, NF-κB, cGAS/STING, ERK, AKT, STAT) and TME-targeting strategies (e.g., fibroblast activation protein inhibitors, exosomes, nanomedicine, immunotherapy) were identified.

Conclusions:

• Complex RT-TME interactions significantly influence RT efficacy.
• Novel TME-targeting approaches show promise for overcoming RT resistance.
• Further research utilizing advanced methods like AI and bioengineering is needed to refine treatment strategies.