TTFields Therapy With Calcium Channel Blockers Against Tumor Fibrosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The increase in IL11 expression due to Tumor Treating Fields (TTFields) treatment leads to fibrosis, which decreases the conductivity and power loss density in tumors, reducing the effectiveness of TTFields treatment.
Innovation Solution
Inhibit IL11 activity or fibrosis using calcium channel blockers such as Felodipine, Verapamil, Diltiazem, and Nifedipine, or combine TTFields with anti-fibrotic agents like sorafenib to maintain high conductivity and enhance TTFields efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TTFields treatment is applied to tumors, then cancer cell growth is inhibited, but fibrosis increases leading to decreased conductivity and reduced treatment effectiveness
Solution Approach 1:
The patent converts the harmful effect of fibrosis (which reduces conductivity and treatment effectiveness) into a beneficial outcome by using calcium channel blockers to inhibit fibrosis. This allows the TTFields treatment to maintain high conductivity and continue effectively killing cancer cells, thus transforming the problematic fibrosis response into a controlled parameter that enhances overall treatment reliability
2Reliability
If TTFields treatment is applied to tumors, then cancer cell growth is inhibited, but conductivity decreases due to fibrosis
Solution Approach 1:
The patent introduces calcium channel blockers as an intermediary substance that mediates between the TTFields treatment and the tumor tissue. This intermediary prevents the fibrosis-induced conductivity decrease by blocking calcium channels that would otherwise promote fibrotic changes, thereby maintaining the electrical conductivity necessary for effective TTFields treatment
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Inhibiting IL11 or fibrosis maintains high conductivity, ensuring the effectiveness of TTFields treatment by reducing tumor volume and fibrosis.
Implementation Method 1
TTFields are low intensity (e.g., 1-3 V/cm) alternating electric fields within the intermediate frequency range (e.g., 100-500 kHz) that inhibit cancer cell growth
Implementation Method 2
the fibrosis inhibitor comprises a calcium channel blocker
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
A reduction in viability of cancer cells (e.g., glioblastoma) and a reduction in tumor volume can be achieved by applying a 100-500 kHz (e.g., 200 kHz) alternating electric field to the cancer cells and inhibiting IL11 (interleukin-11) activity and optionally administering and anti-fibrotic agent. The inhibiting of IL11 activity may be accomplished, for example, by decreasing IL11 expression, inhibiting IL11 signaling, downregulating IL11, neutralizing IL11, blocking an IL11 receptor, administering an IL11 antagonist, administering an IL11 neutralizing antibody, or administering an IL11 receptor α (IL11Ra) neutralizing antibody.