Glioblastoma Therapy: Past, Present and Future.
Elena ObradorPaz Moreno-MurcianoMaría Oriol-CaballoRafael López-BlanchBegoña PinedaJulia Lara Gutiérrez-ArroyoAlba LorasLuis G Gonzalez-BonetConrado Martinez-CadenasJosé M EstrelaMaría Ángeles Marqués-TorrejónPublished in: International journal of molecular sciences (2024)
Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16 ink4 , TP53/MDM2/P14 arf , PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood-brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.
Keyphrases
- pi k akt
- signaling pathway
- stem cells
- immune response
- clinical trial
- free survival
- dna damage
- healthcare
- gene expression
- end stage renal disease
- randomized controlled trial
- minimally invasive
- chronic kidney disease
- palliative care
- newly diagnosed
- dendritic cells
- white matter
- toll like receptor
- low dose
- blood brain barrier
- young adults
- high resolution
- health insurance
- bone marrow
- induced apoptosis
- pain management
- radiation induced
- cancer therapy
- drug delivery
- study protocol
- high speed
- childhood cancer