Treatment of cancer/inhibition of metastasis

Abstract

Substances and methods are disclosed for reducing or preventing metastatic behaviour in VGSC expressing cancer by the effect of at least reducing the persistent part of the voltage gated sodium channel current without eliminating the transient part. Inhibition of metastatic cell behaviours such as detachability, lateral motility, transverse migration and invasiveness is demonstrated using the known drugs ranolazine and riluzole.

Description

BACKGROUND[0001]This invention relates to the treatment of cancer, and is particularly, but not exclusively, concerned with the treatment of metastatic cancer, such as breast or prostate cancer.[0002]Progression of metastatic cancer, such as breast and prostate cancer, is generally considered as comprising five phases, as follows:[0003]1. Genesis, namely the initial transformation of a normal cell into a cancer cell.[0004]2. Proliferation, namely increase in the number of cancer cells to form a primary tumour of increasing size.[0005]3. Switching, during the genesis or proliferation phase, from a condition in which the cancer cells have no potential for metastatic behaviour to a condition in which they do.[0006]4. Detachment of cancer cells from the primary tumour followed by movement of those detached cells into surrounding regions of tissue within the same organ towards the circulation system.[0007]5. Metastasis, namely the movement of the detached cells through the circulation (b...

AI Technical Summary

Benefits of technology

[0023]However, in accordance with an aspect of the invention, metastatic behaviour is inhibited or reduced in cancer by administering ranolazine or riluzole, or another substance, at an appropriate dosage to inhibit or reduce the persistent part of the VGSC current without blocking, or at least without completely blocking, the transient part. Thus, metastasis in cancer may be inhibited or reduced in this way without having to administer doses of drugs which would be fatal.

[0026]The fact that metastatic behaviour may be inhibited or reduced without causing cell death may be a significant advantage since recent work has suggested that treating cancer by killing the cells may, at least in some cases, be counter-productive in the sense that whilst there will be a short term benefit, the cancer will nevertheless return and proliferate. Thus, the invention provides the possibility of inhibiting or preventing metastatic behaviour without the potential problems which may arise from actually killing the cancer cells.

[0037]As more fully described below, experiments carried out in connection with this invention have shown that administering ranolazine or riluzole at various dosage levels can increase the adhesiveness of the cells and / or reduce one or more of the lateral motility, transverse migration and invasiveness of the cells.

[0040](a) that breast and prostate cancer (and other cancers in which VGSCs are expressed) can be contained so that the patient may be able to live with such cancer without serious detriment;

[0041](b) as a result, the need for the patient to undergo aggressive treatments to destroy the cancerous cells, such as by chemo or radiotherapy may be avoided;

[0045](f) since ranolazine and riluzole have been on the market and approved for human use for many years, the invention can be put into clinical use without having to go through all the lengthy testing for side effects etc.

Problems solved by technology

Doses of these, or any other drug, which would have the effect of completely blocking VGSC currents in cardiac tissue would be fatal to the patient because the heart requires these currents in order to carry out its function.

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