Identification of fluocinolone acetonide to prevent paclitaxel-induced peripheral neuropathy.
Paclitaxel (PTX) is among the most commonly used cancer drugs that cause chemotherapy-induced peripheral neuropathy (CIPN), a debilitating and serious dose-limiting side effect. Currently, no drugs exist to prevent CIPN, and symptomatic therapy is often ineffective. In order to identify therapeutic candidates to prevent axonal degeneration induced by PTX, we carried out a phenotypic drug screening using primary rodent dorsal root ganglion sensory neurons. We identified fluocinolone acetonide as a neuroprotective compound and verified it through secondary screens. Furthermore, we showed its efficacy in a mouse model of PTX-induced peripheral neuropathy and confirmed with four different cancer cell lines that fluocinolone acetonide does not interfere with PTX's antitumor activity. Our study identifies fluocinolone acetonide as a potential therapy to prevent CIPN caused by PTX.
Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.|Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Aysel
A
Cetinkaya-Fisgin
Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Min Geol
MG
Joo
Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore.
Xiang
X
Ping
Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore.|Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Nitish V
NV
Thakor
Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.
Cengizhan
C
Ozturk
Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Ahmet
A
Hoke
Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore.|Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
In Hong
IH
Yang
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D001369:Axons / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D005446:Fluocinolone Acetonide / Q000494:pharmacology / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D017239:Paclitaxel / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D005446:Fluocinolone Acetonide; D017239:Paclitaxel
chemotherapy-induced peripheral neuropathy; fluocinolone acetonide; paclitaxel; phenotypic drug screening