Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood-brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients.

Keywords: drug delivery systems; glioblastoma multiforme; immunotherapy; nanomedicine; resistance.

Figure 1

Traditional therapies for GBM.

Figure 2

The depiction of the characteristic of a healthy BBB versus a disrupted BBB in GBM (created by Bio Render).

Figure 3

Immunotherapy and precision therapy approaches of GBM tumors. (Adapted with permission from Ref. [219]. 2020 American Cancer Society).