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- オンデマンド講演会
過去の講演会
第307回 川崎医学会講演会
| :: 日 時 | 平成26年11月12日（水） 17:00・18:00 |
| :: 場 所 | 図書館小講堂 |
| :: 座 長 | 岸 文雄 |
「Targeting the metastasis suppressor,
NDRG1: A new class of therapeutics
for cancer treatment」
Des R. Richardson
B.Sc., M.Sc., Ph.D., D.Sc. (UWA),
F.F.Sc. (RCPA), FRCPath (UK)
Professor of Cancer Cell Biology,
University of Sydney NHMRC Senior
Principal Research Fellow
Novel chemotherapeutics with marked and selective antitumor activity are essential to develop, particularly those that can overcome resistance to established therapies. Iron (Fe) is critical for cell-cycle progression and DNA synthesis and potentially represents a novel molecular target for the design of new anticancer agents.
Our studies over the last 30 years have led to the development of a new class of Fe chelators for cancer therapy. These compounds have recently been commercialised to enable their entrance into clinical trials resulting in the companies, Oncochel Therapeutics LLC (San Francisco, USA) and Oncochel Therapeutics Pty Ltd (Australia; see http://colmeddev.com/7.html).
These agents show broad antitumor activity and could overcome resistance to established antitumor agents. The in vivo efficacy of the most effective chelator identified, di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT), was assessed by using a panel of human xenografts in nude mice. After 7 weeks, net growth of a melanoma xenograft in Dp44mT-treated mice was only 8% of that in mice treated with vehicle. In addition, no differences in these latter animals were found in hematological indices between Dp44mT-treated mice and controls. No marked systemic Fe depletion was observed comparing Dp44mT- and vehicle-treated mice, probably because of the very low doses required to induce anticancer activity.
Dp44mT caused up-regulation of the Fe-responsive tumor growth and metastasis suppressor Ndrg1 in the tumor but not in the liver, indicating a potential mechanism of selective anticancer activity (Richardson et al. PNAS USA 2006;103:14901-6). The potent and selective anti-metastastic activity of Dp44mT in animal models have been independently verified by others (EMBO Mol. Med. 2012;4:93-108).
Collectively, these results indicate that the novel Fe chelators have potent and broad antitumor activity and can overcome resistance to established chemotherapeutics because of their unique mechanism of action. Moreover, they can inhibit metastasis through up-regulation of NDRG1. This latter effect is crucial, as 90% of deaths due to cancer are because of metastasis to vital organs.