Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities

Abstract

Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways. Although EGFR inhibitors have demonstrated efficacy in other cancers, their application in glioblastoma is hindered by blood–brain barrier penetration and intrinsic resistance. The evolving realm of nanodrugs and convection-enhanced delivery offers promise in ensuring precise drug delivery to the brain. Critical to success is the identification of glioblastoma patient populations that benefit from EGFR inhibitors. Tools like radiolabeled anti-EGFR antibody 806i facilitate the visualization of EGFR conformations, aiding in tailored treatment selection. Recognizing the synergistic potential of combination therapies with downstream targets like mTOR, PI3k, and HDACs is pivotal for enhancing EGFR inhibitor efficacy. In conclusion, the era of precision oncology holds promise for targeting EGFR in glioblastoma, contingent on tailored treatments, effective blood–brain barrier navigation, and the exploration of synergistic therapies.

The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells

“…This might be another relevant strategy for tumor cells to induce migration since immune cells, including activated monocytes/macrophages, comprise a significant amount of cells in GBM tumors. However, ODZ1 has not been linked to the epidermal growth factor receptor (EGFR), a key player in tumor malignancy in several cancer types, including GBM, and a target for therapeutic interventions [10]. A recent work described tumor regression in two patients with GBM treated with a CAR-T strategy engineered to target EGFRvIII, as well as wild-type EGFR [11].…”

“…Although the responses were transient, the study sheds light on the potential of this technology against main biomarkers in GBM and highlights the relevance of the EGFR as a key target. Other therapeutic strategies, including EGFR inhibitors, have not achieved the same degree of success seen in other cancers, partly due to the blood-brain barrier and intrinsic resistance [10,12]. Thus, deciphering potential paths forward to target the EGFR pathway may open new opportunities for therapies against GBM.…”