ALK-FGFR Combination Therapy Suppresses Resistance in Cancer
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Solution Overview
Problem
ALK fusion gene-positive cancer often develops resistance to ALK inhibitors, limiting their effectiveness over time, and there is a need for therapies that can suppress the acquisition of resistance.
Innovation Solution
A combination therapy using an ALK inhibitor and a FGFR kinase inhibitor is administered to ALK fusion gene-positive cancer cells that are positive for FGFR1 and FGF2 expression at baseline, to enhance growth suppression and prevent resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ALK inhibitor is administered alone, then initial cancer growth suppression is achieved, but resistance develops over time
Solution Approach 1:
The patent combines ALK inhibitor with FGFR kinase inhibitor in a fixed-combination formulation to simultaneously target both ALK and FGFR signaling pathways. This merging of two therapeutic agents addresses the resistance problem by blocking alternative signaling routes that cancer cells use to evade single-agent therapy, thereby maintaining prolonged treatment effectiveness.
Solution Approach 2:
The invention creates a composite pharmaceutical product containing both ALK inhibitor and FGFR kinase inhibitor in defined ratios. This composite formulation enables dual-pathway inhibition within a single therapeutic regimen, preventing resistance development through synergistic action while simplifying administration compared to separate therapies.
2Reliability
If combination therapy with ALK inhibitor and FGFR kinase inhibitor is used, then resistance suppression is enhanced, but treatment complexity increases
Solution Approach 1:
The patent merges two separate therapeutic agents into a single fixed-combination product with defined dosage ratios. This approach maintains the therapeutic benefits of dual-pathway inhibition for resistance suppression while reducing treatment complexity by eliminating the need for separate prescribing, dosing, and monitoring of two individual medications.
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
The combination therapy demonstrates an excellent growth suppressive effect on ALK fusion gene-positive cancer cells and effectively suppresses the acquisition of resistance, prolonging progression-free survival.
Implementation Method 1
Alectinib (generic name: alectinib hydrochloride) is approved in Japan and overseas as an ALK inhibitor. FGFR inhibitors are known to suppress the phosphorylation of the FGFR kinase, thereby suppressing the growth of cancer cells
Data Source
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AI summary
The present invention relates to a drug for treating or preventing ALK fusion gene-positive cancer positive for FGFR1 expression and positive for FGF2 expression at baseline, the drug comprising a compound having ALK inhibitory activity and a FGFR inhibitor in combination, a combination agent, a pharmaceutical composition, a preparation, a treatment or prevention method, or a drug for suppressing acquisition of resistance, a method for selecting a patient, and the like.