Cancer Signaling Pathway Profiling for Personalized Therapy Selection
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Solution Overview
Problem
Current therapeutic strategies for cancers such as glioma and colorectal cancer lack patient stratification, leading to suboptimal treatment outcomes, with anti-angiogenic drugs like Bevacizumab showing modest efficacy in only a fraction of patients.
Innovation Solution
A method to determine therapeutically targetable dominant signaling pathways in cancer samples by analyzing gene expression levels and calculating scores, allowing for personalized treatment protocols based on the identification of key pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If anti-angiogenic drugs like Bevacizumab are used as standard treatment, then treatment coverage is improved, but treatment efficacy deteriorates because only 30-60% of patients respond and median progression-free survival reaches only 6 months
Solution Approach 1:
The patent segments the glioblastoma patient population into distinct molecular subtypes based on gene expression profiles (e.g., VEGF-high, EGFR-high, PDGFRA-high subtypes). This segmentation allows identification of specific patient groups who are most likely to respond to anti-angiogenic therapy versus other targeted therapies, thereby improving treatment efficacy by matching the right therapy to the right patient subtype rather than applying uniform treatment to all patients
Solution Approach 2:
The patent performs preliminary molecular characterization of tumors through gene expression analysis before initiating treatment. By determining the dominant signaling pathway activation status in advance, clinicians can pre-select the most appropriate therapeutic strategy (anti-angiogenic, anti-EGFR, anti-PDGFRA, etc.), avoiding ineffective treatments and improving overall response rates
2Adaptability or versatility
If gene expression analysis of multiple pathways is performed, then personalized treatment selection is improved, but diagnostic complexity increases
Solution Approach 1:
The patent extracts and focuses analysis on a specific, predefined set of key genes representing major signaling pathways (VEGF, EGFR, PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3) rather than analyzing the entire transcriptome. This extraction approach maintains comprehensive pathway coverage while simplifying the diagnostic process by limiting the number of genes to a manageable panel that can be assessed using standardized techniques
Solution Approach 2:
The patent transforms complex gene expression data into simplified binary or categorical parameters indicating pathway activation status (e.g., high vs. low expression, activated vs. inactive). This parameter transformation converts continuous gene expression measurements into discrete clinical decision parameters that are easier to interpret and apply in routine practice
Data Source
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AI summary
The present invention provides a powerful tool to identify personalized therapeutic strategies. In particular, the invention provides methods for determining therapeutically targetable dominant signaling pathways in a cancer sample from a subject affected with a solid cancer, determining a treatment protocol for the subject, selecting a subject for a therapy, determining whether the subject is susceptible to benefit from a therapy, predicting clinical outcome of the subject, treating the subject and/or predicting the sensitivity of a solid cancer to a therapy.