Method of Treating Cancer, Particularly Malignant Melanoma, Using Dithiocarbamate Derivatives

Dithiocarbarmate, particularly tetraethylthiuram disulfide, strongly inhibits the growth of a variety of cancer cells. The present invention provides a novel strategy for treating cancer, particularly metastatic melanoma, by using disulfiram to reduce tumor growth and to potentiate the effect of other anticancer agents. This invention showed that disulfiram inhibited the DNA binding of transcription factor ATF/CREB, cyclin A expression, cell cycle progression, and melanoma proliferation in vitro and in severe combined immunodeficient (SCID) mice in a metal-dependent manner. Moreover, the inventors reported the first use of oral zinc gluconate and disulfiram at currently approved doses for alcoholism to treat a patient with stage IV ocular melanoma and hepatic metastases. The patient has experienced considerable tumor regression and remains clinically well after 53 continuous months of therapy.

Cancer is a major health problem of the modern medical era and ranks second only to heart disease as a cause of death in the United States. While some types of cancers respond relatively well to current chemotherapeutic antineoplastic drug regimens, other cancers responds poorly to chemotherapy. For example, malignant melanoma is a type of tumor notoriously resistant to radiation and traditional chemotherapeutic agents. Based on the finding that melanoma growth and angiogenesis are sensitive to disulfiram in a metal-dependent fashion, this invention provides a new strategy for treating cancer, particularly metastatic melanoma, by using disulfiram. Also, this new method can be used for sensitizing AIDS/HIV patients to anti-retroviral therapy by locking the P-glycoprotein membrane toxin extrusion pump using neutral dithiocarbamate metal compounds.

Stage of Development
Patents (#6,548,540, #6,589,987, and #6,706,759) have been issued from the U.S. Patent and Trademark Office. Patents have been issued under the PCT with nationalization to Europe (1214063) and Australia (782029). Also, several PCT patent applications are pending in Europe, United States, Japan, Australia, and Canada.
This technology is available for licensing under either exclusive or non-exclusive terms.

Additional Info
*Brar SS, Grigg C, Wilson KS, Holder WD Jr, Dreau D, Austin C, Foster M, Ghio AJ, Whorton AR, Stowell GW, Whittall LB, Whittle RR, White DP, Kennedy TP. (2004) Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol Cancer Ther. 3(9):1049-60.

Inventor(s): Thomas Kennedy

Type of Offer: Licensing

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