Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

Mario Chiariello; Giovanni Inzalaco; Virginia Barone; Lisa Gherardini

doi:10.3389/fncel.2023.1327621

Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

Front Cell Neurosci. 2023 Dec 21:17:1327621. doi: 10.3389/fncel.2023.1327621. eCollection 2023.

Authors

Mario Chiariello^{1

2}, Giovanni Inzalaco^{1

2

3}, Virginia Barone⁴, Lisa Gherardini^{1

2}

Affiliations

¹ Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Via Fiorentina, Siena, Italy.
² Core Research Laboratory (CRL), Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Via Fiorentina, Siena, Italy.
³ Department of Medical Biotechnologies, University of Siena, Siena, Italy.
⁴ Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Abstract

Glioblastoma (GB) is a highly malignant primary brain tumor with limited treatment options and poor prognosis. Despite current treatment approaches, including surgical resection, radiation therapy, and chemotherapy with temozolomide (TMZ), GB remains mostly incurable due to its invasive growth pattern, limited drug penetration beyond the blood-brain barrier (BBB), and resistance to conventional therapies. One of the main challenges in GB treatment is effectively eliminating infiltrating cancer cells that remain in the brain parenchyma after primary tumor resection. We've reviewed the most recent challenges and surveyed the potential strategies aimed at enhancing local treatment outcomes.

Keywords: blood brain barrier; drug repurposing; glioblastoma; local delivery; microenvironment.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of the article. This work was supported by the specific funding from Regione Toscana/Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO) to MC.