CDK4/6 and mtRTKI Combination Therapy for Solid Cancer
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Solution Overview
Problem
There is a need for development of additional safe and proven combinational therapies to treat cancer, as existing treatments often fail to effectively manage solid tumors and can have unpredictable effects.
Innovation Solution
The use of combinations of inhibitors of cyclin-dependent kinases 4 and 6 (CDK 4/6) together with multi-targeted receptor tyrosine kinase inhibitors (mtRTKIs) has been found to provide synergistic therapeutic effects in treating various types of solid tumors, with specific combinations such as palbociclib and sunitinib showing effective tumor control and reduction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy of CDK4/6 inhibitors and mtRTKIs is used, then therapeutic efficacy is improved, but treatment complexity increases
Solution Approach 1:
The patent combines CDK4/6 inhibitors and mtRTKIs into a unified treatment approach, merging two distinct therapeutic mechanisms to achieve synergistic anti-cancer effects. This combination addresses the complexity by integrating complementary pathways that target different aspects of cancer biology simultaneously.
Solution Approach 2:
The combination therapy demonstrates multi-functionality by effectively treating multiple types of solid tumors across different organ systems. The therapeutic regimen serves universal purposes across various cancer types, including breast, lung, colorectal, and other solid tumors, thereby justifying the treatment complexity through broad applicability.
2Adaptability or versatility
If multi-targeted receptor tyrosine kinase inhibitors are used, then signaling pathway coverage is improved, but toxicity increases
Solution Approach 1:
The patent applies local quality by selectively targeting specific signaling pathways (RTKs) that are dysregulated in particular tumor types. The mtRTKI component is chosen and dosed to provide pathway coverage relevant to the specific cancer being treated, thereby reducing unnecessary toxicity from inhibiting pathways that are not relevant to the patient's tumor biology.
Solution Approach 2:
The treatment regimen utilizes parameter changes by adjusting the dose and timing of mtRTKI administration in relation to CDK4/6 inhibitor dosing. By optimizing these parameters, the patent achieves adequate signaling pathway coverage while minimizing peak toxicities that would occur with simultaneous maximum dosing of both agents.
Data Source
AI summary
A method for treating adenoid cystic carcinoma (ACC) is provided, comprising co-administering at least inhibitor of cyclin-dependent kinase 4/6 (CDK 4/6) and at least one multi-targeted receptor tyrosine kinase inhibitor (mtRTKI). The CDK 4/6 inhibitor may be at least one of palbociclib, abemaciclib and ribociclib and the mtRTKI may be at least one of sunitinib, sorafenib and pazopanib. A combination therapy with palbociclib and sunitinib provides a synergic effect in treatment of ACC.