Nanodelivery Systems Targeting Epidermal Growth Factor Receptors for Glioma Management.
Sathishbabu ParanthamanMeghana Goravinahalli ShivananjegowdaManohar MahadevAfrasim MoinShivakumar Hagalavadi NanjappaNandakumar NanjaiyahSaravana Babu ChidambaramDevegowda Vishakante GowdaPublished in: Pharmaceutics (2020)
A paradigm shift in treating the most aggressive and malignant form of glioma is continuously evolving; however, these strategies do not provide a better life and survival index. Currently, neurosurgical debulking, radiotherapy, and chemotherapy are the treatment options available for glioma, but these are non-specific in action. Patients invariably develop resistance to these therapies, leading to recurrence and death. Receptor Tyrosine Kinases (RTKs) are among the most common cell surface proteins in glioma and play a significant role in malignant progression; thus, these are currently being explored as therapeutic targets. RTKs belong to the family of cell surface receptors that are activated by ligands which in turn activates two major downstream signaling pathways via Rapidly Accelerating Sarcoma/mitogen activated protein kinase/extracellular-signal-regulated kinase (Ras/MAPK/ERK) and phosphatidylinositol 3-kinase/a serine/threonine protein kinase/mammalian target of rapamycin (PI3K/AKT/mTOR). These pathways are critically involved in regulating cell proliferation, invasion, metabolism, autophagy, and apoptosis. Dysregulation in these pathways results in uncontrolled glioma cell proliferation, invasion, angiogenesis, and cancer progression. Thus, RTK pathways are considered a potential target in glioma management. This review summarizes the possible risk factors involved in the growth of glioblastoma (GBM). The role of RTKs inhibitors (TKIs) and the intracellular signaling pathways involved, small molecules under clinical trials, and the updates were discussed. We have also compiled information on the outcomes from the various endothelial growth factor receptor (EGFR)-TKIs-based nanoformulations from the preclinical and clinical points of view. Aided by an extensive literature search, we propose the challenges and potential opportunities for future research on EGFR-TKIs-based nanodelivery systems.
Keyphrases
- growth factor
- protein kinase
- signaling pathway
- cell surface
- cell proliferation
- pi k akt
- tyrosine kinase
- small cell lung cancer
- clinical trial
- risk factors
- oxidative stress
- end stage renal disease
- cell death
- epidermal growth factor receptor
- endothelial cells
- radiation therapy
- endoplasmic reticulum stress
- systematic review
- cell cycle
- newly diagnosed
- cell cycle arrest
- induced apoptosis
- chronic kidney disease
- peritoneal dialysis
- cell therapy
- squamous cell
- living cells
- radiation induced
- patient reported