Opportunities and Challenges of Small Molecule Inhibitors in Glioblastoma Treatment: Lessons Learned from Clinical Trials.
Linde HoosemansMarc A VooijsAnn HoebenPublished in: Cancers (2024)
Glioblastoma (GBM) is the most prevalent central nervous system tumour (CNS). Patients with GBM have a dismal prognosis of 15 months, despite an intensive treatment schedule consisting of surgery, chemoradiation and concurrent chemotherapy. In the last decades, many trials have been performed investigating small molecule inhibitors, which target specific genes involved in tumorigenesis. So far, these trials have been unsuccessful, and standard of care for GBM patients has remained the same since 2005. This review gives an overview of trials investigating small molecule inhibitors on their own, combined with chemotherapy or other small molecule inhibitors. We discuss possible resistance mechanisms in GBM, focussing on intra- and intertumoral heterogeneity, bypass mechanisms and the influence of the tumour microenvironment. Moreover, we emphasise how combining inhibitors can help overcome these resistance mechanisms. We also address strategies for improving trial outcomes through modifications to their design. In summary, this review aims to elucidate different resistance mechanisms against small molecule inhibitors, highlighting their significance in the search for novel therapeutic combinations to improve the overall survival of GBM patients.
Keyphrases
- small molecule
- protein protein
- end stage renal disease
- clinical trial
- locally advanced
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- healthcare
- minimally invasive
- coronary artery disease
- radiation therapy
- rectal cancer
- randomized controlled trial
- squamous cell carcinoma
- adipose tissue
- palliative care
- single cell
- blood brain barrier
- quality improvement
- pain management
- weight loss
- insulin resistance