Unlocking the microbial treasure trove: advances in Streptomyces derived secondary metabolites in the battle against cancer.

Streptomyces is widely recognized as the "biological factory" of specialized metabolites comprising a huge variety of bioactive molecules with diverse chemical properties. The potential of this Gram-positive soil bacteria to produce such diversified secondary metabolites with significant biological properties positions them as an ideal candidate for anticancer drug discovery. Some of the Streptomyces-derived secondary metabolites include siderophores (enterobactin, desferrioxamine), antibiotics (xiakemycin, dinactin) pigments (prodigiosin, melanin), and enzymes (L-methioninase, L-asperginase, cholesterol oxidase) which exhibit a pronounced anticancer effect on both in vitro and in vivo system. These secondary metabolites are endowed with antiproliferative, pro-apoptotic, antimetastatic, and antiangiogenic properties, presenting several promising characteristics that make them suitable candidates in the battle against this deadly disease. In this comprehensive review, we have dived deep and explored their history of discovery, their role as anticancer agents, underlying mechanisms, the approaches for the discovery of anticancer molecules from the secondary metabolites of Streptomyces (isolation of Streptomyces, characterization of bacterial strain, screening for anticancer activity and determination of in vitro and in vivo toxicity, structure-activity relationship studies, clinical translation, and drug development studies). The hurdles and challenges associated with this process and their future prospect were also illustrated. This review highlights the efficacy of Streptomyces as a "microbial treasure island" for novel anticancer agents, which warrants sustained research and exploration in this field to disclose more molecules from Streptomyces that are unidentified and to translate the clinical application of these secondary metabolites for cancer patients.