AML Patient Stratification via Kinase Inhibitor Sensitivity Profiling
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Solution Overview
Problem
Current treatment options for acute myeloid leukemia (AML) are limited, with a high rate of relapse and refractoriness to primary treatments, and there is a need for improved methods to identify patients who will respond to kinase pathway inhibitors.
Innovation Solution
Integration of proteomic, kinomic, and genomic profiling to determine the differentiation status of leukemia cells, which serves as a biomarker for sensitivity to kinase pathway inhibitors, allowing for accurate prediction of treatment efficacy and patient stratification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy and radiation therapy are used for AML treatment, then initial response is achieved, but high rate of relapse and refractoriness occurs
Solution Approach 1:
The patent changes the treatment approach from conventional chemotherapy to kinase pathway inhibitors, selecting patients based on specific molecular parameters (kinase mutations, differentiation status). This parameter-based selection and treatment modification addresses the high relapse rate by targeting the specific molecular drivers of AML rather than using non-specific chemotherapy.
Solution Approach 2:
The patent replaces the mechanical/conventional chemotherapy system with a molecularly-targeted kinase inhibitor system. By substituting non-specific cytotoxic therapy with specific kinase pathway inhibition based on molecular profiling, the treatment achieves more durable responses and reduces refractoriness.
2Reliability
If kinase pathway inhibitors are used for AML treatment, then treatment specificity is improved, but identification of responsive patients is difficult
Solution Approach 1:
The patent performs preliminary molecular profiling and differentiation status assessment before initiating kinase pathway inhibitor therapy. By pre-identifying patients with appropriate molecular characteristics (kinase mutations, advanced differentiation status), the system ensures that only responsive patients receive the targeted therapy, eliminating the need for difficult post-treatment responsiveness assessment.
Solution Approach 2:
The patent introduces molecular profiling and differentiation status as intermediary markers that mediate between the kinase pathway inhibitor and the patient's leukemia cells. These intermediaries (molecular markers, differentiation status) provide a reliable mechanism to identify responsive patients without requiring direct measurement of treatment response.
3Measurement precision
If comprehensive molecular profiling is performed to identify responsive patients, then treatment accuracy is improved, but diagnostic complexity increases
Solution Approach 1:
The patent segments the complex diagnostic process into distinct, manageable components: molecular profiling (identifying kinase mutations) and differentiation status assessment (evaluating cellular maturity). By dividing the comprehensive evaluation into these separate, standardized segments, the system achieves high stratification accuracy while managing diagnostic complexity through structured approach.
Data Source
AI summary
The invention relates to the treatment of acute myeloid leukaemia (AML) in patients. In particular, the invention concerns improved methods for identifying AML patients who may be effectively treated with kinase pathway inhibitors, and improved methods for predicting whether a kinase pathway inhibitor may be efficacious for treatment of AML in an individual patient. The invention also comprehends a method of screening a plurality of patients suffering from acute myeloid leukaemia, to determine whether the acute myeloid leukaemia of any one or more of the patients may be effectively treated with a kinase pathway inhibitor. The invention further provides methods for the treatment of such patients with kinase pathway inhibitors, and kinase pathway inhibitors for use in such methods.