Drug Repurposing in Medulloblastoma: Challenges and Recommendations
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Neuro-oncology (GJ Lesser, Section Editor)
Drug Repurposing in Medulloblastoma: Challenges and Recommendations Hussein Hammoud, MSc1 Zahraa Saker, MSc1 Hayat Harati, PhD1 Youssef Fares, MD, PhD1,2 Hisham F. Bahmad, MD, MSc3,4,* Sanaa Nabha, PhD1,* Address *,1 Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Hadas, Beirut, Lebanon Email: [email protected] 2 Department of Neurosurgery, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon 3 Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL, 33140, USA *,4 Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA Email: [email protected]
* Springer Science+Business Media, LLC, part of Springer Nature 2020
Hussein Hammoud and Zahraa Saker are authors who contributed equally to this work as co-first authors. Hisham F. Bahmad and Sanaa Nabha are authors who contributed equally to this work as co-senior authors. This article is part of the Topical Collection on Neuro-oncology Keywords Medulloblastoma I Drug repurposing I Signaling pathway I Therapeutic targets
Opinion statement Medulloblastoma is the most frequently diagnosed primary malignant brain tumor among children. Currently available therapeutic strategies are based on surgical resection, chemotherapy, and/or radiotherapy. However, majority of patients quickly develop therapeutic resistance and are often left with long-term therapy-related side effects and sequelae. Therefore, there remains a dire need to develop more effective therapeutics to overcome the acquired resistance to currently available therapies. Unfortunately, the process of developing novel anti-neoplastic drugs from bench to bedside is highly time-consuming and very expensive. A wide range of drugs that are already in clinical use for treating non-
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Curr. Treat. Options in Oncol.
(2021) 22:6
cancerous diseases might commonly target tumor-associated signaling pathways as well and hence be of interest in treating different cancers. This is referred to as drug repurposing or repositioning. In medulloblastoma, drug repurposing has recently gained a remarkable interest as an alternative therapy to overcome therapy resistance, wherein existing non-tumor drugs are being tested for their potential anti-neoplastic effects outside the scope of their original use.
Introduction Medulloblastoma (MB) is the most frequently diagnosed primary malignant brain tumor diagnosed in children [1], accounting for around a quarter of all pediatric central nervous system (CNS) neoplasms [2]. It is a highly aggressive tumor that usually develops early during embryonic life [3•]. It mainly originates from the cerebellar vermis and thus primarily affects children in their first year of life [4]. Studies have shown that MB arises from remnants of the primitive neuroectoderm within the germinal matrix of the fourth ventricle roof [5,6] or from the external granular layer precursor cells [7,8].
It is appro
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