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Int. J. Mol. Sci. 2018, 19(12), 3905;

Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development

Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Department of General and Specialized Surgery, Antonio Pedro University Hospital, Fluminense Federal University, Niterói, RJ 24220, Brazil
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Authors to whom correspondence should be addressed.
Received: 20 September 2018 / Revised: 26 November 2018 / Accepted: 4 December 2018 / Published: 6 December 2018
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Intracranial malignancies, such as primary brain cancers and brain-localized metastases derived from peripheral cancers, are particularly difficult to treat with therapeutic agents, because the blood-brain barrier (BBB) effectively minimizes brain entry of the vast majority of agents arriving from the systemic circulation. Intranasal administration of cancer drugs has the potential to reach the brain via direct nose-to-brain transport, thereby circumventing the obstacle posed by the BBB. However, in the field of cancer therapy, there is a paucity of studies reporting positive results with this type of approach. A remarkable exception is the natural compound perillyl alcohol (POH). Its potent anticancer activity was convincingly established in preclinical studies, but it nonetheless failed in subsequent clinical trials, where it was given orally and displayed hard-to-tolerate gastrointestinal side effects. Intriguingly, when switched to intranasal delivery, POH yielded highly promising activity in recurrent glioma patients and was well tolerated. As of 2018, POH is the only intranasally delivered compound in the field of cancer therapy (outside of cancer pain) that has advanced to active clinical trials. In the following, we will introduce this compound, summarize its molecular mechanisms of action, and present the latest data on its clinical evaluation as an intranasally administered agent for glioma. View Full-Text
Keywords: intranasal; perillyl alcohol; temozolomide intranasal; perillyl alcohol; temozolomide

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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 (CC BY 4.0).

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Chen, T.C.; Da Fonseca, C.O.; Schönthal, A.H. Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development. Int. J. Mol. Sci. 2018, 19, 3905.

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