Integrating NOTCH Inhibitors with Standard Chemotherapeutic Drugs in Glioblastoma Multiforme Treatment: A Synergistic Approach

Author(s):

Abdul Hadi Khan*

Glioblastoma Multiforme (GBM) presents a significant obstacle in the field of cancer because of its aggressive nature and limited treatment options. Despite advances in surgical resection, radiation therapy, and chemotherapy, the median survival rate remains dishearteningly brief at 15 months. Glioblastoma Stem Cells (GSCs), particularly those expressing the CD133 marker, are acknowledged for their pivotal role in tumor growth and resistance to conventional therapies. The NOTCH signaling pathway is a crucial regulator of GSCs and plays a significant role in the induction of tumor heterogeneity and radioresistance. In this review, we explore the therapeutic potential of the NOTCH signaling pathway and evaluate various classes of NOTCH inhibitors inhibitors such as Gamma-Secretase Inhibitors (GSI), small interfering RNA (siRNA), and monoclonal antibodies. Although recent trials have suggested improved outcomes by integrating GSIs with standard treatments, the challenge persists in sparing CD133⁺ cells. This review also emphasizes the role of Chk1 and Chk3 inhibitors in reversing radioresistance in CD133⁺ cells. In conclusion, this review explores the nuances of NOTCH signaling inhibition in GBM treatment, emphasizing precision in targeting the tumor microenvironment and addressing therapeutic resistance associated with CD13⁺ cells.