Combination chemotherapy compositions and methods

Abstract

This invention relates to combination therapies involving anticancer chemotherapeutic agents and isoflavones or analogues thereof. The invention flier relates to compounds, compositions, methods and therapeutic uses involving, containing, comprising, including and / or for preparing platinum-isoflavonoid complexes suitable for use in the combination therapies of the invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a Continuation-In-Part of U.S. application Ser. No. 10 / 530,176, filed Mar. 9, 2006; which is a 371 of PCT / AU03 / 01296, filed Oct. 2, 2003; the disclosures of each of which are incorporated herein by reference.FIELD OF THE INVENTION [0002] This invention relates to combination therapies involving anticancer chemotherapeutic agents and isoflavones or analogues thereof. The invention further relates to compounds, compositions, methods and therapeutic uses involving, containing, comprising, including and / or for preparing platinum-isoflavonoid complexes suitable for use in the combination therapies of the invention. BACKGROUND [0003] The regulation of cell division (mitosis) is of critical importance to the normal growth and development of a multicellular organism, as well as the homeostatic maintenance of tissues, and the ability of certain cell types to respond appropriately to environmental cues. [0004] Oncogenesis is t...

AI Technical Summary

Benefits of technology

[0019] According to an aspect of the present invention there is provided a method of increasing the sensitivity of cancer cells or a tumour to a chemotherapeutic agent by contacting said cells or tumour with an isoflavonoid compound of formula (I) as set out below.

[0051] According to a further aspect of the present invention there is provided a method for increasing the sensitivity of melanoma cells or a melanoma to a chemotherapeutic agent by contacting said cells or melanoma with an isoflavonoid compound of formula (I).

Problems solved by technology

Those cells containing aberrant genetic information may undergo clonal expansion and act as a site for additional genetic alteration, at which time uncontrolled proliferation results in the formation of a neoplasm.

Localised, chronic irritation or inflammation can also cause cells to divide abnormally, resulting in abnormal growths or cellular masses, or tumours.

Predicting the responsiveness of a given tumour-related disease type to a particular drug is difficult, as each disease type is different and may respond to different treatments.

Cisplatin is active against proliferating or cancerous cells by binding to DNA and interfering with its repair mechanism, eventually leading to cell death.

The adducts or cisplatin-DNA complexes attract the attention of DNA repair proteins which become irreversibly bound, The resulting distortion to the shape of the DNA by the binding of cisplatin prevents effective repair and hence, cell death.

Patients undergoing cancer chemotherapy often have to contend with quite severe and debilitating side effects due to the toxicity of the active agents.

Common side effects of chemotherapy are nausea and vomiting.

Chemotherapy regimes are further complicated by the efficacy of currently available chemotherapeutic agents against various cancers or other tumour types sometimes being insufficient.

Further, some therapeutic or prophylactic agents exert side effects, or can induce the development of tolerance in abnormally dividing cells during clinical use, leading to a situation in which certain tumour types become multiply drug resistant.

Multidrug resistance thus remains a main complication of long-term successful tumour chemotherapy.

However, melanoma is typically resistant to standard chemotherapy and radiation therapy.

A number of chemotherapeutic agents, including platinum-based and taxane drugs have been used to treat melanoma but with disappointing response rates.

Our understanding of the resistance mechanisms employed by melanoma to avoid the cytotoxic effects of conventional therapeutics is limited, as is our ability to devise alternative therapeutics to overcome resistance.” The increased incidence of melanoma, compounded by the lack of effective therapy, in particular once the disease has metastasized, underscores the need for improved methods of treating patients with melanoma.

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