Exploiting signal transduction pathways for cancer therapy: insights from natural products in preclinical models

Genetic or epigenetic changes that lead to abnormal development of signalling through cellular pathways such as MAPK, PI3K/AKT/mTOR, Wnt/β-catenin play an important role in driving cancer. These signalling pathways control how cells grow, divide and die (apoptosis). Thus, the continued activation of these pathways represents a characteristic of oncogenesis as well as a suitable target for treatment. This review will highlight how natural products have been shown to modify the molecular pathways involved with these signalling cascades in preclinical cancer models. Data derived from an array of preclinical studies showcase how the bioactive phytochemicals that comprise these products are implemented in the form of targeting cancer cells through specific inhibition of signalling pathways, induction of apoptosis, inhibition of tumour growth and alteration of oncogenic crosstalk. Despite the significant body of evidence, there are still several limitations that exist in regards to variability between studies in terms of the methods used for validation of the mechanism by which these compounds function, differences in their bioavailability and overall robustness of those studies. Using a pathway-centered understanding of the mechanisms by which natural compounds exert their therapeutic effects will support the development of targeted phytopharmaceutical approaches and promote the integration of these therapies into evidence-based oncology practices.