Mechanism-Driven and Clinically Focused Development of Botanical Foods as Multitarget Anticancer Medicine: Collective Perspectives and Insights from Preclinical Studies, IND Applications and Early-Phase Clinical Trials

SIMPLE SUMMARY: In this review, we have conducted an extensive literature review and have drawn from our collective experiences to outline critical insights in designing preclinical studies for botanical foods as anticancer investigational new drug (IND) applications as well as to highlight the critical criteria when initiating early-phase clinical trials for botanical food products. This review is for those who wish to understand how botanical foods and their derivatives can contribute to cancer pathobiology, as well as to develop relevant therapeutic approaches to treat cancer by conducting clinically oriented and evidence-based translational studies under United States Food and Drug Administration (USFDA) regulatory frameworks. ABSTRACT: Cancer progression and mortality remain challenging because of current obstacles and limitations in cancer treatment. Continuous efforts are being made to explore complementary and alternative approaches to alleviate the suffering of cancer patients. Epidemiological and nutritional studies have indicated that consuming botanical foods is linked to a lower risk of cancer incidence and/or improved cancer prognosis after diagnosis. From these observations, a variety of preclinical and clinical studies have been carried out to evaluate the potential of botanical food products as anticancer medicines. Unfortunately, many investigations have been poorly designed, and encouraging preclinical results have not been translated into clinical success. Botanical products contain a wide variety of chemicals, making them more difficult to study than traditional drugs. In this review, with the consideration of the regulatory framework of the USFDA, we share our collective experiences and lessons learned from 20 years of defining anticancer foods, focusing on the critical aspects of preclinical studies that are required for an IND application, as well as the checkpoints needed for early-phase clinical trials. We recommend a developmental pipeline that is based on mechanisms and clinical considerations.