Anticancer Secondary Metabolites Produced by Fungi: Potential and Representative Compounds

Cancer remains one of the leading causes of death worldwide, and resistance to conventional therapies underscores the need for the discovery of novel antitumor agents. The ongoing search for novel natural sources offers promising avenues for discovering unique anticancer compounds with new mechanisms of action. One of these natural sources is represented by fungi, a prolific group of endophytic and non-endophytic eukaryotes able to produce bioactive secondary metabolites, many of which exhibit potent antitumor properties. These natural compounds display diverse chemical structures including polyketides, terpenoids, alkaloids, amino acid-derived compounds, phenols, etc. Their mechanisms of action are equally varied, ranging from induction of apoptosis and cell cycle arrest to inhibition of angiogenesis and metastasis. In this review we describe some potential antitumor compounds of fungal origin, together with the characteristics and biosynthesis of three representative types of antitumor compounds produced by filamentous fungi: squalene-derived sterol-type antitumor agents, prenylated diketopiperazine antitumor metabolites and meroterpenoid antitumor compounds. The ongoing scientific debate regarding the presence of paclitaxel biosynthetic genes in fungi is also discussed. As drug resistance remains a challenge in cancer therapy, fungal compounds offer a valuable reservoir for the development of new chemotherapeutic agents with novel modes of action.