A03：Relationship between platinum-based chemotherapeutic drug-induced peripheral neuropathy and biometal disturbance in the sensory neurons
Takayuki NAKAGAWA
（Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital）
Lab website
Platinum-based chemotherapeutic drugs are widely used to treat various cancers, but frequently induce sensory disturbance, such as peripheral neuropathy or taste disturbance. These adverse events are the most frequently-observed metal toxicity in clinic and diminish the quality of life and activities of daily living in patients with cancer. Nevertheless, there are no or little effective strategies for preventing or treating them. Sensory nerve system is composed of various cells, such as several types of sensory neurons, which can distinctively detect each sensation, myelin-forming Schwann cells and so on. However, uptake and accumulation of platinum, vulnerability to platinum-neurotoxicity, and correlation with the symptoms induced by sensory disturbance in each cell type remain unclear. In this study project, we will investigate the kinetics of metals including platinum, especially sensory nerve type-specific accumulation of platinum and the disturbance of biometal homeostasis in the sensory nerve system, and analyze their role and mechanism to platinum neurotoxicity-induced sensory disturbance.
Major publications
Miyake T, Nakamura S, Zhao M, So K, Inoue K, Numata T, Takahashi N, Shirakawa H, Mori Y, Nakagawa T*, Kaneko S
“Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS”
Nat Commun 7: 12840 (2016)
doi: 10.1038/ncomms12840
Miyake T, Nakamura S, Zhao M, Hamano S, Inoue K, Numata T, Takahashi N, Nagayasu K, Shirakawa H, Mori Y, Nakagawa T*, Kaneko S
“Distinct mechanism of cysteine oxidation-dependent activation and cold sensitization of human transient receptor potential ankyrin 1 channel by high and low oxaliplatin”
Front Physiol 8: 878 (2017)
doi: 10.3389/fphys.2017.00878
Imai S, Koyanagi M, Azimi Z, Nakazato Y, Matsumoto M, Ogihara T, Yonezawa A, Omura T, Nakagawa S, Wakatsuki S, Araki T, Kaneko S, Nakagawa T*, Matsubara K
“Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms”
Sci Rep 7: 5947 (2017)
doi: 10.1038/s41598-017-05784-1
Ogihara T, Nakagawa T*, Hayashi M, Koyanagi M, Yonezawa A, Omura T, Nakagawa S, Kitada N, Imai S, Matsubara K
“Improvement of peripheral vascular impairment by a phosphodiesterase type 5 inhibitor tadalafil prevents oxaliplatin-induced peripheral neuropathy in mice”
J Pharmacol Sci 141: 131-138 (2019)
doi: 10.1016/j.jphs.2019.10.005
Yamashita K, Ogihara T, Hayashi M, Nakagawa T, Ishizaki Y, Kume M, Yano I, Niigata R, Hiraoka J, Yasui H, Nakamura T
“Association between dexamethasone treatment and alterations in serum concentrations of trace metals”
Pharmazie, in press