BACKGROUND

Most treatment plans for patients with cancer include surgery, radiation therapy, and/or chemotherapy. Early clinical trials were performed for the use of vitamin C (ascorbic acid) to treat cancer. But epidemiological studies evaluating the association between the intake of vitamin C and cancer risk produced inconsistent results. (Luo, et al., Association between vitamin C intake and lung cancer: a dose-response meta-analysis, Sci Rep. 2014 Aug. 22; 4:6161). Other studies determined that no significant differences were noted between the ascorbate-treated and placebo-treated groups for symptoms, performance status, or survival (Moertel C G, Fleming T R, Creagan E T, Rubin J, O'Connell M J, Ames M M. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med. 1985; 312(3):137-41; Creagan E T, Moertel C G, O'Fallon J R, Schutt A J, O'Connell M J, Rubin J, Frytak S. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med. 1979; 301(13):687-90). There is a need for more efficacious cancer treatments with minimal side effects.

SUMMARY

The present invention provides in certain embodiments a method of treating a hyperproliferative disorder associated with high intracellular iron comprising administering pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof. As used herein the term “high iron” means that the intracellular free iron concentration is greater than the in a corresponding non-tumor cell.

The present invention provides in certain embodiments a method of reducing toxic effects of melphalan in a patient in need thereof comprising administering pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof.

The present invention provides in certain embodiments a method of treating multiple myeloma, including smoldering multiple myeloma, comprising administering pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof.

The present invention provides in certain embodiments a use of the combination of pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof and melphalan in the preparation of a medicament for the treatment of a hyperproliferative disorder in a mammal.

The present invention provides in certain embodiments a kit comprising pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof and melphalan, a container, and a package insert or label indicating the administration of the PAA and with melphalan for treating a hyperproliferative disorder.

The present invention provides in certain embodiments a product comprising pharmacological ascorbic acid (PAA) and melphalan as a combined preparation for separate, simultaneous or sequential use in the treatment of a hyperproliferative disorder.

The present invention provides in certain embodiments a therapeutic composition comprising a combination of (a) pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof; and (b) an alkylating agent. In certain embodiments, the therapeutic composition lacks a chelator, such as ethylene diamine tetraacetic acid (EDTA).

The present invention provides in certain embodiments, a method of administering to a mammalian cell having downregulated expression of Ferroportin 1 (Fpn1) as compared with its normal counterpart cell an expression-modulating agent, comprising contacting the mammalian cell with pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof.

The present invention provides in certain embodiments, a method of administering to a mammalian cell having upregulated expression of enhancer of zeste 2 (EZH2) as compared with its normal counterpart cell an expression-modulating agent, comprising contacting the mammalian cell with an inhibitor of EZH2.

The present invention provides in certain embodiments, a method of administering to a mammalian cell having upregulated expression of Thyroid Hormone Receptor Interactor Protein 13 (TRIP13) as compared with its normal counterpart cell an expression-modulating agent, comprising contacting the mammalian cell with pharmacological ascorbic acid (PAA) or a pharmaceutically acceptable salt thereof and/or with an inhibitor of TRIP13.

