Validating Inferred Anticancer Pathways via Patient-Derived Cell Interrogation
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Solution Overview
Problem
Current methods for predicting anticancer drug responses based on genomic and omics information lack validation with real-world clinical data, necessitating a method to optimize anticancer therapies by validating predicted drug sensitivities using actual patient data.
Innovation Solution
A method involving obtaining tumor-associated samples, generating omics data, applying it to a pathway analysis engine for predicting tumor cell sensitivity, and validating the predictions by interrogating enriched viable tumor cells with pharmaceutically active compounds, measuring anticancer activity, and generating a validation metric for treatment planning.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If computational modeling methods (PARADIGM, DIRPP) are used to predict anticancer drug responses based on omics data, then drug sensitivity predictions can be generated, but the predictions lack validation with real-world clinical data
Solution Approach 1:
The patent implements feedback by comparing in silico predicted drug responses with actual in vitro experimental results from patient-derived tumor cells. The validation metric generated from this comparison provides feedback to assess and improve the reliability of computational predictions, closing the loop between theoretical modeling and empirical verification.
Solution Approach 2:
The patent introduces patient-derived viable tumor cells as an intermediary between computational predictions and clinical outcomes. These cells serve as a bridging system that can be tested in vitro with predicted effective drugs, translating silico predictions into measurable biological responses before clinical application.
2Adaptability or versatility
If probabilistic pathway models are used to assess drug effectiveness, then drug sensitivity can be predicted, but the method remains unvalidated without clinical data
Solution Approach 1:
The patent performs preliminary validation by testing predicted drug responses in patient-derived tumor cells before clinical treatment. This preliminary experimental verification ensures that the probabilistic pathway model predictions are reliable and adapted to the specific patient's tumor characteristics before actual clinical application.
Solution Approach 2:
The validation metric generated by comparing predicted versus observed drug responses provides feedback to refine and adapt the probabilistic pathway models for individual patients, improving both reliability and adaptability of drug response assessments.
3Loss of information
If in silico pathway analysis is used to identify genetic parameters for drug response, then treatment predictions can be made, but the predictions lack real-world verification
Solution Approach 1:
The patent uses patient-derived viable tumor cells as an intermediary to verify genetic parameter predictions. These cells retain the patient's specific genetic characteristics and can be experimentally tested with predicted effective drugs, providing real-world verification of in silico genetic analysis without losing important biological context.
Data Source
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AI summary
The invention provides a method of validating a predicted pathway activity of a pathway in a solid tumor of a subject, with a digital computer, the method comprising : a) obtaining a tumor associated sample from the subject; b) obtaining omics data from the tumor associated sample obtained in (a); c) applying the omics data obtained in (b) to a digital computer programmed with a pathway analysis engine configured to generate predicted tumor cell pathway activities in silico, to provide a prediction of one or more pharmaceutically active anticancer compounds effective for treating the subject's tumor; d) obtaining enriched viable tumor cells from the subject, and interrogating the enriched viable tumor cells with at least one pharmaceutically active compound known to interact with a pathway element of one or more of the pathways predicted by (c), to measure anticancer activity of the at least one pharmaceutically active compound with respect to the subject's enriched viable tumor cells.