Integrating NOTCH Inhibitors with Standard Chemotherapeutic Drugs in
Glioblastoma Multiforme Treatment: A Synergistic Approach
Abstract
Glioblastoma multiforme (GBM) presents a significant obstacle in the
field of cancer therapy because of its aggressiveness and limited
treatment options. Despite advances in surgical resection, radiation
therapy, and chemotherapy, the median survival remains dishearteningly
brief at 15 months. This review focuses on the mysterious Glioblastoma
stem cells (GSCs), particularly those expressing the CD133 marker,
acknowledged for their pivotal role in tumor growth and resistance to
conventional therapies. The NOTCH signaling pathway emerges as a
promising target. This review explores the NOTCH signaling pathway, a
crucial regulator of GSCs, and evaluates inhibitors like gamma-secretase
inhibitors (GSI), siRNA, and monoclonal antibodies. While recent trials
suggest improved outcomes by integrating GSIs with standard treatments,
the challenge persists in sparing CD133-positive cells. This review also
emphasizes the role of Chk1 and Chk3 inhibitors in the reversal of
radioresistance in CD133+ cells. In summary, 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 CD133-positive cells.