Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening

SIMPLE SUMMARY: Increasing numbers of cancer patients are turning to complementary and alternative medicines (CAM) to facilitate or replace their cancer treatments, or they are obtaining natural products in their diet. This is concerning, as there is evidence of molecular interactions between these bioactive compounds and cancer drugs that can impede or reverse their efficacy and prevent cancer regression. High-throughput drug screening and deep learning techniques have successfully been applied in the past to evaluate synergistic cancer drug and natural product combinations. However, these techniques should be applied more commonly in the context of drug antagonism to uncover potentially harmful interactions and drive safer recommendations for cancer patients. In this review, we evaluate the antagonistic interactions between natural products and chemotherapeutics and highlight how the application of high-throughput screening and deep learning techniques can strengthen this area of research. ABSTRACT: Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.