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Treatment of cancer/inhibition of metastasis

a technology of metastasis and cancer, applied in the field of cancer treatment, can solve the problems that patients' doses of these or any other drugs, which would have the effect of completely blocking vgsc currents in cardiac tissue, and would be fatal to patients, and achieve the effect of reducing the number of cells

Inactive Publication Date: 2013-08-08
DJAMGOZ MUSTAFA B A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention relates to a method of reducing or inhibiting metastasis in cancer without causing cell death. This is achieved by administering a substance called ranolazine or riluzole at a suitable dosage to block the persistent part of the VGSC current while leaving the transient part unobstructed. This approach has been shown to increase the adhesiveness of cells and reduce their motility, invasiveness, and lateral movement. This method may be useful for containing breast and prostate cancer in patients, reducing the need for aggressive treatments and potentially improving the chances of survival. Since ranolazine and riluzole have been on the market for many years and have been shown to have minimal side effects, this invention may be easily integrated into clinical practice.

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.

Method used

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  • Treatment of cancer/inhibition of metastasis
  • Treatment of cancer/inhibition of metastasis
  • Treatment of cancer/inhibition of metastasis

Examples

Experimental program
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Effect test

example 1

Effects of Chemical Hypoxia on the Single-Cell Adhesion of MDA-MB-231 Cells

[0132]Chemical hypoxia was induced by treating cells with different concentrations of hydrogen peroxide for 24 hours. Single-cell adhesion was measured using the technique described above and illustrated in FIG. 4. The change in detachment negative pressure (ΔDNP) was expressed as a percentage versus a control population of untreated cells. Hypoxia reduced the cell adhesion and increasing the concentration of hydrogen peroxide, i.e., increasing the degree of hypoxia, led to greater reduction in cell adhesion as shown in FIG. 8. In this figure, the vertical axis represents the change in detachment negative pressure (ΔDNP), increasing downwardly so that a higher negative value is indicative of a cell's lower adhesion and, hence, its tendency to detachment. The horizontal axis is a logarithmic scale of hydrogen peroxide concentration, increasing from left to right.

[0133]Human breast cancer cells from the MDA-MB-...

example 2

Effects of Ranolazine on the Single-Cell Adhesion of MDA-MB-231 Cells Under Normoxic and Hypoxic Conditions

[0135]Single-cell adhesion was measured using the technique described above and illustrated in FIG. 4 for human MDA-MB-231 cells exposed to different concentrations of ranolazine and under normoxic and hypoxic conditions. Ranolazine increased the substrate adhesion of cells under normoxia in a dose dependent manner. The dose-dependent increase in the adhesion of cells was even more marked under hypoxia—See FIG. 9. In this figure, the vertical axis represents a measure of the adhesion of cells. The horizontal axis is a logarithmic scale of ranolazine concentration, increasing from left to right. Data were collected from n=7 independent experiments for each condition and are presented in FIG. 9 as means±SEM.

[0136]Human breast cancer cells from the MDA-MB-231 cell line were plated in cell culture dishes at a density of 2.5×104 cells / ml and left to settle for 48 hours prior to meas...

example 3

Effects of Ranolazine on the Lateral Motility of MDA-MB-231 Cells Under Normoxia and Hypoxia

[0140]Lateral motility of the cells was measured using the technique described above and illustrated in FIG. 5.

[0141]Referring to FIG. 10, the vertical axis represents the motility index of the measured cells, with a reference point for normal motility being represented by the control sample (block 1001 of the histogram) of MDA-MB-231 cells under normoxia and without drug, normalised to 100%. Across the horizontal axis, the set of results for experiments conducted under normoxia is plotted on the left-hand side and the set of results for experiments conducted under hypoxia is plotted on the right-hand side. For each set of results, the concentration of ranolazine used increases from left to right.

[0142]Block 1005 is the result obtained for the control sample (without drug) for MDA-MB-231 cells under conditions of hypoxia. From a comparison of blocks 1001 and 1005 it can be seen that hypoxia i...

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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...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07D277/82C07D241/04
CPCA61K31/00A61K31/428C07D277/82C07D241/04A61K31/495A61K31/138A61K31/167A61K31/19A61K31/4458C07D295/15A61P35/04A61P13/08A61P15/00A61P43/00
Inventor DJAMGOZ, MUSTAFA BILGIN ALI
Owner DJAMGOZ MUSTAFA B A
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