Seek and Destroy: The Use of Natural Compounds for Targeting the Molecular Roots of Cancer

One of the major issues facing anticancer research relies on the intrinsic inability of tumor cells to undergo apoptosis. Additionally, the development of cancer resistance to standard therapy and the great heterogeneity associated with frequent mutations and epigenetic changes make an ever increasing challenge to achieve treatment success. Thus, novel therapeutic approaches to induce cancer demise must be explored. Compelling evidence has shown the ability of naturally-occurring compounds to modulate signal transduction pathways, apoptosis and cell cycle progression, supporting their relevance to anticancer drug discovery. Moreover, millions of years of biological selection have led to an unlimited repertoire of chemical structures unmatched by any synthetic combinatorial library and recent advances in the fields of chemistry and biology are uncovering this still underexplored source of new promising natural agents, opening novel perspectives for the development of alternative strategies to fight cancer. This review presents the current status of natural products in modern oncology, illustrating the importance of some old and new agents, such as antimitotics and apoptosis inducers, as candidates of pharmacological interest in drug development and/or as chemical tools for the elucidation, as well as targeting, of deregulated cancer signaling pathways. Finally, some aspects of chemical modifications done in natural products core aiming to improve their activity and/or effectiveness will be discussed.