Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Extracellular vesicles (EVs) are key mediators of intercellular communication in solid tumors.
• EVs transfer proteins, nucleic acids, lipids, and metabolites, influencing tumor evolution, microenvironment remodeling, immune regulation, and stress responses.
• EV production is an adaptive process linked to intracellular trafficking and metabolic programs, not a constitutive secretory event.

Purpose of the Study:

• To critically examine extracellular vesicle (EV) biology in solid tumors.
• To connect EV biogenesis, trafficking, lipid metabolism, and heterogeneity with engineering strategies.
• To discuss barriers limiting the clinical translation of EV-based diagnostics and therapeutics.

Main Methods:

• Review of current scientific literature on EV biology in solid tumors.
• Analysis of EV biogenesis, trafficking, lipid metabolism, and functional heterogeneity.
• Examination of EV engineering strategies (source selection, surface modification, cargo loading, hybrid approaches).
• Discussion of challenges in clinical translation (heterogeneity, isolation variability, manufacturing, regulation).

Main Results:

• EV functions in tumors are context-dependent and vary across tumor types, stages, and experimental systems.
• EV heterogeneity, plasticity, and context-dependent cargo sorting present challenges but also opportunities for therapeutic engineering.
• Significant barriers remain for clinical translation, including biological and isolation variability, incomplete mechanistic understanding, scalability, and regulatory standardization.

Conclusions:

• Extracellular vesicles (EVs) play a complex role in solid tumor progression and response to therapy.
• Engineering EVs offers promising avenues for diagnostics and therapeutics, but requires addressing significant biological and technical challenges.
• A balanced assessment of opportunities and limitations is essential for advancing EV-based clinical applications.