4.6 Review

Current state and future perspective of drug repurposing in malignant glioma

Journal

SEMINARS IN CANCER BIOLOGY
Volume 68, Issue -, Pages 92-104

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2019.10.018

Keywords

Drug repurposing; Malignant glioma; Glioblastoma; Drug cocktail; Multi-targeting

Categories

Funding

  1. NIH NINDS [K08 NS083732, R01 NS095848, R01 NS102366]

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Malignant gliomas are difficult to treat due to their invasive nature and resistance to adjuvant therapies. Drug repurposing is a promising approach to discover new treatments for these tumors, as it can accelerate the process and utilize existing drugs with known safety profiles.
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.

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