A comprehensive review on chemistry and pharmacology of marine bioactives as antimetastatic agents

Abstract

Metastasis by and large is responsible for the worldwide deaths associated with various types of cancers. The metastatic variant of cancer cells generated due to the cellular heterogeneity and abnormal activation of various signaling pathways in the tumor population leads to the progressive colonization of cancer cells in various organs. Over the years there has been a constant effort towards developing effective therapeutic strategies for the treatment and prevention of metastasis. The current conventional therapies have lacked efficacy due to the complex nature of metastasis involving multistep processes comprising tumor-tumor and tumor–extracellular matrix adhesion molecules, EMT, proteases, and tumor developing cell pathways. Albeit the exact mechanism of metastasis is somewhat still uncertain, there are a few recognized targets such as EMT markers, MMPs, serine proteases, microtubulin, angiogenic markers, and anoikis resistance, that have been identified as potential therapeutic targets for the inhibition of metastatic progression of cancer cells. Marine biodiversity offers unique chemical compounds due to the exposure to stressful environments for the discovery of novel bioactive compounds that are highly specific to these therapeutic targets. The review discusses various natural and semisynthetic compounds of marine origin having antimetastatic potential, focusing on the isolation, underlying mechanism of inhibition of multiple signaling pathways, and structural modification of isolated compounds for further development as drug candidates having superior clinical translation potential.