Small-molecule mTOR inhibitors in the clinic: From bench to bedside

As a central modulator of cellular proliferation, metabolic processes, and immunological functions, the mechanistic target of rapamycin (mTOR) signaling pathway has emerged as an attractive therapeutic focus for managing diverse pathological conditions, including cancer, autoimmune disorders, and organ transplant rejection. mTOR inhibitors, initially identified in the context of cancer therapy, have shown efficacy in regulating immune responses and preventing abnormal cell proliferation. Pharmacological investigations spanning preclinical models to human subjects reveal mTOR-targeting agents possess immunomodulatory properties concurrent with antitumor effects, evidenced by multicenter clinical studies documenting improved progression-free survival rates and delayed oncological recurrence in epithelial-derived and hematopoietic malignancies. This review explores the development of mTOR inhibitors, tracing their journey from early laboratory discoveries to clinical application, and emphasizes their role in transforming the therapeutic landscape for a range of diseases.