Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Frontiers in Anti-cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-angiogenic Add-on Therapy in Glioblastoma

Laura Guarnaccia
,
Stefania Elena Navone
ORCID logo ,
Matteo Maria Masseroli
,
Melissa Balsamo
ORCID logo ,
Manuela Caroli
,
Silvia Valtorta
ORCID logo ,
Rosa Maria Moresco
,
Rolando Campanella
,
Emanuele Garzia
,
Laura Riboni
ORCID logo ,
Giovanni Marfia
* ,
Marco Locatelli
Version 1 : Received: 26 November 2021 / Approved: 29 November 2021 / Online: 29 November 2021 (12:30:08 CET)

A peer-reviewed article of this Preprint also exists.

Guarnaccia, L.; Marfia, G.; Masseroli, M.M.; Navone, S.E.; Balsamo, M.; Caroli, M.; Valtorta, S.; Moresco, R.M.; Campanella, R.; Garzia, E.; Riboni, L.; Locatelli, M. Frontiers in Anti-Cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-Angiogenic Add-On Therapy in Glioblastoma. Cancers 2022, 14, 112. Guarnaccia, L.; Marfia, G.; Masseroli, M.M.; Navone, S.E.; Balsamo, M.; Caroli, M.; Valtorta, S.; Moresco, R.M.; Campanella, R.; Garzia, E.; Riboni, L.; Locatelli, M. Frontiers in Anti-Cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-Angiogenic Add-On Therapy in Glioblastoma. Cancers 2022, 14, 112.

Abstract

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

Keywords

brain tumors; glioblastoma; angiogenesis; metformin

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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