A Potential Zinc Treatment for Patients with Terminal Advanced Laryngeal or Tongue Carcinoma: Clioquinol Zinc Ionophore

Laryngeal and tongue squamous cell carcinomas account for an estimated 37,000 cases and 7,000 deaths/year in the U.S. The localized lesions are generally treated by surgical resection, and/or radiation therapy. When progression to metastases occurs, a systemic chemotherapy is necessary. An efficacious medication has not been available; largely due to the absence of information regarding the development and progression of those malignancies. Consequently, potential targets for successful chemotherapy are not identified. Since decreased zinc has been implicated in the development and treatment of all other carcinomas, it likely exists in laryngeal and tongue squamous cell carcinomas. This report demonstrates that zinc is decreased in these malignancies when compared to the normal cells; and is likely due to the downregulation of their functional ZIP-family zinc-uptake transporter. The reason is that the higher zinc level in the normal cells is cytotoxic in the malignant cells. Therefore, a chemotherapy that restores the higher zinc levels will be cytotoxic in the malignant cells. To achieve this, we employed clioquinol zinc ionophore to facilitate the uptake and accumulation of zinc. The treatment inhibited proliferation of HN4 laryngeal carcinoma cells and HN6 tongue carcinoma cells. That is consistent with other reports that collectively demonstrate that all carcinomas are “ZIP-deficient/decreased zinc” malignancies; and can be terminated by a treatment, such as clioquinol, to facilitate the uptake of cytotoxic levels of zinc. It is now necessary to establish the efficacy of the clioquinol treatment for human laryngeal and tongue tumors under in vivo conditions in xenograft implants in animals; and ultimately in human clinical trials. A case report of the first successful treatment of a patient with terminal advanced prostate carcinoma had included clioquinol. It is reasonable to expect that clioquinol treatment could be the first chemotherapy for terminating tongue and laryngeal squamous cell carcinomas.