CAM Assay Screening for Anti-Angiogenic Resistance
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Solution Overview
Problem
Current anti-angiogenic therapies for cancer and debilitating diseases face challenges due to elevated levels of endogenous pro-angiogenic thyroid hormones, which can lead to resistance, rendering treatments ineffective.
Innovation Solution
A method involving a Chick Chorioallantoic Membrane (CAM) assay to screen patients for resistance by analyzing vessel branch formation in the presence of anti-angiogenic agents, followed by inducing subclinical hypothyroidism and administering anti-angiogenic agents that bind to the integrin αvβ3 receptor, along with chemotherapeutic or anti-inflammatory agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-angiogenic therapy is administered to treat cancer, then tumor growth is inhibited, but resistance develops due to elevated endogenous thyroid hormones
Solution Approach 1:
The patent converts the harmful effect of endogenous thyroid hormones (which promote angiogenesis and cause treatment resistance) into a beneficial diagnostic marker. By measuring thyroid hormone levels in patient samples, the system identifies patients at risk of developing resistance, allowing for proactive intervention before treatment failure occurs.
Solution Approach 2:
The patent implements preliminary screening of patient samples for elevated thyroid hormone levels before initiating anti-angiogenic therapy. This preliminary action identifies patients who are at risk of developing resistance, enabling clinicians to take preventive measures such as adjusting treatment protocols or adding complementary therapies before resistance develops during treatment.
2Measurement precision
If screening assays are developed to detect resistance, then patient selection improves, but assay complexity and cost increase
Solution Approach 1:
The patent extracts and measures specific thyroid hormone components (such as T3, T4, or their metabolites) from patient blood or tissue samples using targeted analytical methods. By focusing on specific hormone molecules rather than performing comprehensive proteomic or metabolomic profiling, the system achieves high measurement precision for resistance detection while maintaining relatively simple assay protocols that can be implemented in standard clinical laboratories.
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
This approach effectively identifies and mitigates resistance to anti-angiogenic treatments by reducing the levels of pro-angiogenic hormones, enhancing the efficacy of anti-angiogenic therapy and preventing resistance development.
Implementation Method 1
A novel cell surface, integrin αvβ3 receptor for endogenous thyroid hormone (L-thyroxine, T4, T3) has been identified. The αvβ3 receiver however, is not a homologue of the nuclear thyroid hormone receptor (TR), but rather, a cell surface receptor that is capable of performing a number of nucleus-mediated events
Implementation Method 2
In the absence of thyroid hormone, tetrac blocks the angiogenic activity of basic fibroblast growth factor (bFGF, FGF2), vascular endothelial growth factor (VEGF) and other pro-angiogenic factors
Data Source
AI summary
A method for screening a patient for angioinhibition resistance and treating said patient having a disease susceptible to treatment via an anti-angiogenic agent. The screening method includes an assay for identifying the presence of angioinhibition resistance in patients by collecting patient blood or serum and subjecting it to a Chick Chorioallantoic Membrane (CAM) angiogenesis assay configured for accepting a human tumor wherein the human tumor xenograft includes a vasculature system. The screening method and assay further includes steps that include using the CAM results for identifying the endogenous pro-angiogenic non-peptide hormone concentrations of the blood sample by calculating the vascular activity of the vasculature system of the human tumor xenograft in the presence of anti-angiogenic drugs and inducing in the patient, a state of subclinical hypothyroidism prior to commencing anti-angiogenic treatment.