Nanodelivery Systems Targeting Epidermal Growth Factor Receptors for Glioma Management

Abstract

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.

Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

“…This non-specificity can lead to deleterious effects on normal cells as well. A possible solution to this challenge can be TKIs-based nanodelivery systems, that will specifically target tumor cells [38]. Another common challenge faced by any anticancer drug is the induction of chemo-resistance during therapy.…”

Fabrication and Characterization of Paclitaxel and Resveratrol Loaded Soluplus Polymeric Nanoparticles for Improved BBB Penetration for Glioma Management

“…The novel drug delivery systems are used to enhance the efficacy and increase the solubility of therapeutic agents [ 11 ]. Drug loaded nanoparticles are an efficient and non-invasive technique to treat cerebral diseases.…”

“…Drug loaded nanoparticles are an efficient and non-invasive technique to treat cerebral diseases. Polymeric Nanoparticles (PNPs) are found to be the most likely drug nano carriers due to their excellent biocompatibility, targeting ability, enhanced residence time and convenient formulation technique [ 7 , 11 ].…”

“…Therefore, there is an urgent need to find a novel anticancer drug which has higher therapeutic index and efficiency for a glioma treatment [10]. The novel drug delivery systems are used to enhance the efficacy and increase the solubility of therapeutic agents [11]. Drug loaded nanoparticles are an efficient and noninvasive technique to treat cerebral diseases.…”

Novel Anticancer Strategies

“…Low drug solubility, blood–brain barrier penetration, and drug–target residence time are major issues in translating in vitro potency to in vivo efficacy for glioblastoma treatment. In their review, Paranthaman et al describe the molecular basis of glioblastoma, emphasizing the role of receptor tyrosine kinases (RTKs) and small molecules under clinical trials, and provide an updated research literature and future guidelines on epidermal growth factor receptor (EGFR)-RTK inhibitors-based nanodelivery systems [ 4 ].…”