Advances in Brain Cancer Therapy: Exploration of Small Molecules and Nanomedicine

Abstract

Brain cancer remains one of the most challenging malignancies of the central nervous system, with high recurrence rates and poor prognosis posing a serious threat to patient survival. Current therapeutic approaches, including surgery, radiotherapy, and chemotherapy, have improved survival to some extent but remain limited by the blood–brain barrier (BBB), tumor heterogeneity, and drug resistance. In recent years, small-molecule drugs and nanomedicine-based delivery systems have shown great potential in overcoming these barriers. Small molecules such as temozolomide (TMZ) and targeted agents play important roles in combination therapies, yet issues of BBB penetration and resistance persist. Nanomedicine platforms—including liposomes, polymeric nanoparticles, micelles, and exosomes—enable enhanced drug accumulation at tumor sites and controlled release, offering new strategies to break through the limitations of conventional therapies. However, clinical translation faces challenges related to safety, regulatory approval, and high costs. Looking ahead, emerging technologies such as artificial intelligence–driven drug discovery, CRISPR-based gene editing, liquid biopsy for early detection, and theranostics (therapy combined with diagnostics) hold promise for more precise and personalized treatment of brain cancer. This review summarizes the current therapeutic strategies and limitations of brain cancer, highlights advances in small-molecule and nanomedicine approaches, and discusses challenges and future perspectives for their clinical translation.