ALK and CDK Inhibitor Combination Therapy for Resistant NSCLC
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Solution Overview
Problem
There is a need for effective and safe therapeutic agents and combination therapies for treating cancer, particularly for overcoming resistance mechanisms and improving efficacy beyond single-agent treatments.
Innovation Solution
Combining an anaplastic lymphoma kinase (ALK) inhibitor, such as lorlatinib, with a cyclin-dependent kinase (CDK) inhibitor, like palbociclib or PF-06873600, to treat cancers, including non-small cell lung cancer (NSCLC), by administering them sequentially, simultaneously, or concurrently, with the potential for synergistic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If single-agent ALK inhibitor therapy is used, then treatment simplicity is maintained, but treatment efficacy is limited and resistance develops
Solution Approach 1:
The patent combines ALK inhibitors with CDK4/6 inhibitors in a single therapeutic regimen, merging two distinct molecular target pathways (ALK signaling and cell cycle regulation) to achieve synergistic anti-tumor effects while overcoming resistance mechanisms that limit single-agent therapy
2Reliability
If combination therapy with multiple agents is used, then treatment efficacy is improved, but drug-drug interactions and side effects increase
Solution Approach 1:
The patent optimizes dosing parameters and administration schedules for the combination regimen, adjusting the dosage levels and timing of ALK inhibitors and CDK4/6 inhibitors to maximize therapeutic efficacy while minimizing toxic interactions and adverse events
3Duration of action of moving object
If ALK inhibitor monotherapy is used, then dosing schedule simplicity is maintained, but resistance mechanisms limit long-term efficacy
Solution Approach 1:
The patent employs CDK4/6 inhibitors to preemptively block cell cycle progression pathways that cancer cells may use to escape ALK inhibitor-mediated apoptosis, preventing resistance development before it occurs and extending the duration of therapeutic response
Data Source
AI summary
This invention relates to combination therapies comprising an inhibitor of anaplastic lymphoma kinase (ALK) and, an inhibitor of cyclin dependent kinase 4 and 6 (CDK4/6 inhibitor) or an inhibitor of cyclin dependent kinase 2, 4 and 6 (CDK2/4/6 inhibitor), and associated methods of treatment, combinations, pharmaceutical compositions and uses thereof.