Regulation of cancer cell signaling pathways by mushrooms and their bioactive molecules: Overview of the journey from benchtop to clinical trials.

Mushrooms represent a tremendous source of biologically useful and pharmacologically active molecules. Recent breakthroughs in cancer genetics, genomics, proteomics and translational research have helped us to develop a better understanding of the underlying mechanisms which are contributory in cancer development and progression. Different signaling pathways particularly, Wnt, SHH, TGF/SMAD and JAK/STAT have been shown to modulate cancer progression and development. Increasingly it is being realized that genetic/epigenetic mutations and loss of apoptosis also mandate a 'multi-molecular' perspective for the development of therapies to treat cancer. In this review we attempted to provide an overview of the regulation of different signaling pathways by mushrooms and their bioactive compounds. Regulation of Wnt and JAK-STAT pathways by mushrooms is deeply studied but we do not have comprehensive information about regulation of TGF/SMAD, Notch and TRAIL induced signaling pathways because of superficially available data. There are outstanding questions related to modulation of oncogenic and tumor suppressor microRNAs by mushrooms in different cancers. Therefore, detailed mechanistic insights related to targeting of multiple pathways by extracts or bioactive compounds from mushrooms will be helpful in bridging our current knowledge gaps and translation of medicinally precious bioactive molecules to clinically effective therapeutics.