Alternative Models for Anticancer Drug Discovery From Natural Products Using Binary Tumor-Microenvironment-on-a-Chip

Area of Science:

• Biomedical Engineering
• Pharmacology
• Cancer Research

Background:

• Traditional anticancer drug evaluation relies on animal models, which are inefficient and ethically concerning.
• There is a critical need for advanced preclinical platforms to assess drug efficacy and toxicity more effectively.
• Natural products are a promising source of novel anticancer agents, but their development requires robust assessment tools.

Purpose of the Study:

• To introduce and validate a binary tumor-microenvironment-on-a-chip (T-MOC) system for evaluating anticancer drugs.
• To assess the therapeutic potential and toxicity of illudin S and roridin E using the developed T-MOC model.
• To explore the predictive capabilities of the T-MOC system for drug delivery, distribution, and microenvironmental influences.

Main Methods:

• Development of a binary T-MOC system integrating vascular and invasive ductal carcinoma compartments.
• Assessment of illudin S and roridin E, cytotoxic compounds from Omphalotus japonicus and Podostroma cornu-damae, respectively.
• Morphological analysis to predict drug delivery, distribution, and microenvironmental effects on drug response.

Main Results:

• Illudin S showed strong anticancer effects but significant lung and liver toxicity, indicating a narrow therapeutic window.
• Roridin E exhibited potent activity at low doses but high toxicity, particularly in the liver and skin.
• The T-MOC model revealed anisotropic remission and the impact of microenvironmental factors on drug response.

Conclusions:

• The binary T-MOC system serves as a promising alternative to animal models for preclinical anticancer drug evaluation.
• This platform facilitates efficient validation of natural product-derived anticancer agents like illudin S and roridin E.
• The T-MOC system aids in understanding drug delivery barriers, toxicity, and microenvironmental influences, optimizing drug development.