VGSC Persistent Current Inhibition for Metastasis Control
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Solution Overview
Problem
Current treatments for preventing metastasis in cancers like breast and prostate cancer focus on blocking or killing voltage-gated sodium channels (VGSCs), which can be fatal due to the channels' essential role in cardiac function, and may lead to cancer recurrence.
Innovation Solution
Administer ranolazine or riluzole at specific dosages to inhibit the persistent part of VGSC currents in breast and prostate cancer cells without blocking the transient part, reducing metastatic behavior without causing cell death.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of ranolazine or riluzole are administered to completely block VGSC currents, then metastatic behavior is inhibited, but cardiac function is severely impaired leading to fatal outcomes
Solution Approach 1:
The patent applies partial action by selectively inhibiting only the persistent component of VGSC current while preserving the transient component. This is achieved through specific dosing regimens of ranolazine or riluzole that target the low-level sustained current responsible for metastatic behavior without completely blocking the high-amplitude transient current essential for cardiac function. The selective partial inhibition resolves the contradiction by achieving therapeutic effect with sub-toxic dosing.
Solution Approach 2:
The patent changes the parameter of drug dosage from high (complete block) to low/moderate (partial block), and specifically targets the persistent current component rather than the total current. This parameter change allows differentiation between the therapeutic target (persistent current) and the protected function (transient current), enabling metastasis prevention without cardiac toxicity.
2Reliability
If VGSC currents are completely blocked to prevent metastasis, then cancer cell invasion is inhibited, but normal physiological functions are disrupted
Solution Approach 1:
The patent segments the VGSC current into two distinct components: transient current and persistent current. By identifying and targeting only the persistent component for inhibition, the patent preserves the transient component's essential physiological functions while preventing metastatic behavior. This segmentation allows selective therapeutic action without broad physiological disruption.
Solution Approach 2:
The patent applies local quality by creating differential effects on different current components within the same channel system. The persistent current is selectively inhibited in cancer cells to prevent metastasis, while the transient current maintains normal cardiac and neuronal function. This localized selective inhibition resolves the contradiction between therapeutic efficacy and physiological compatibility.
3Reliability
If aggressive treatments are used to kill cancer cells, then tumor growth is controlled, but cancer recurrence occurs and patient quality of life deteriorates
Solution Approach 1:
The patent applies preliminary action by targeting the persistent VGSC current that enables metastatic potential in cancer cells before complete tumor development or recurrence occurs. By inhibiting the persistent current component, the treatment prevents the switch from benign to malignant behavior and blocks invasive potential early, serving as a preventive measure against future recurrence rather than merely treating established aggressive disease.
Data Source
AI summary
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.