Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.

Aldolase enzymes, particularly ALDOA, ALDOB, and ALDOC, play a crucial role in the development and progression of cancer. While the aldolase family is mainly known for its involvement in the glycolysis pathway, these enzymes also have various pathological and physiological functions through distinct signaling pathways such as Wnt/β-catenin, EGFR/MAPK, Akt, and HIF-1α. This has garnered increased attention in recent years and shed light on other sides of this enzyme. Potential therapeutic strategies targeting aldolases include using siRNA, inhibitors like naphthol AS-E phosphate and TX-2098, and natural compounds such as HDPS-4II and L-carnosine. Additionally, anticancer peptides derived from ALDOA, like P04, can potentially increase cancer cells' sensitivity to chemotherapy. Aldolases also affect cancer drug resistance by different approaches, making them good therapeutic targets. In this review, we extensively explore the role of aldolase enzymes in various types of cancers in proliferation, invasion, migration, and drug resistance; we also significantly explore the possible treatment considering aldolase function.