Bioactive Microbial Metabolites in Cancer Therapeutics: Mining, Repurposing, and Their Molecular Targets

The persistence and resurgence of cancer, characterized by abnormal cell growth and differentiation, continues to be a serious public health concern critically affecting public health, social life, and the global economy. Hundreds of putative drug molecules of synthetic and natural origin were approved for anticancer therapy in the last few decades. Although conventional anticancer treatment strategies have promising aspects, several factors such as their limitations, drug resistance, and side effects associated with them demand more effort in repositioning or developing novel therapeutic regimens. The rich heritage of microbial bioactive components remains instrumental in providing novel avenues for cancer therapeutics. Actinobacteria, Firmicutes, and fungi have a plethora of bioactive compounds, which received attention for their efficacy in cancer treatment targeting different pathways responsible for abnormal cell growth and differentiation. Yet the full potential remains underexplored to date, and novel compounds from such microbes are reported regularly. In addition, the advent of computational tools has further augmented the mining of microbial secondary metabolites and identifying their molecular targets in cancer cells. Furthermore, the drug-repurposing strategy has facilitated the use of approved drugs of microbial origin in regulating cancer cell growth and progression. The wide diversity of microbial compounds, different mining approaches, and multiple modes of action warrant further investigations on the current status of microbial metabolites in cancer therapeutics. Hence, in this review, we have critically discussed the untapped potential of microbial products in mitigating cancer progression. The review also summarizes the impact of drug repurposing in cancer therapy and discusses the novel avenues for future therapeutic drug development against cancer.