MEK and SRC Inhibitor Combination for Colorectal Cancer Treatment
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Solution Overview
Problem
Current treatments for colorectal cancer (CRC) are limited and ineffective, with less than 10% of oncology treatments that demonstrate efficacy in pre-clinical models translating to clinical success, and existing in vitro and in vivo models fail to accurately predict patient response due to the complexity of the tumor microenvironment.
Innovation Solution
A combination therapy using a Mitogen/extracellular signal-regulated kinase (MEK) inhibitor and a SRC Proto-Oncogene, Non-Receptor Tyrosine Kinase (SRC) inhibitor is administered to subjects with high SRC p419 levels and no KRAS G12 mutation, tested in an ex-vivo organ culture (EVOC) model to determine efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional in vitro models are used for preclinical studies, then the models are simple and easy to operate, but they fail to recapitulate tumor architecture and complexity leading to poor prediction of patient response
Solution Approach 1:
The patent introduces an ex vivo organ culture system as an intermediary between simple in vitro models and complex in vivo models. This system uses patient-derived organoids cultured in a controlled environment, maintaining tumor architecture and microenvironment complexity while allowing for standardized, controllable experimental conditions. The organoids serve as a mediator that preserves biological fidelity without requiring whole animal models.
2Reliability
If in vivo mouse models are used to predict patient response, then the models capture tumor complexity, but they still fail to accurately predict clinical outcomes with less than 10% translation rate
Solution Approach 1:
The patent creates accurate copies of patient tumors using organoid technology. These organoids are generated by culturing patient-derived cells under controlled conditions to recreate the original tumor's architectural and functional characteristics. The copied tumor models allow testing of multiple therapeutic regimens before clinical application, providing more reliable prediction of patient response without requiring complex in vivo models for every experimental condition.
3Reliability
If combination therapy with MEK inhibitor and SRC inhibitor is administered, then treatment efficacy is improved for patients with high SRC p419 and no KRAS G12 mutation, but treatment complexity and patient selection requirements increase
Solution Approach 1:
The patent applies local quality by tailoring the treatment approach to specific patient subgroups based on their molecular characteristics. Patients with high SRC p419 expression and absence of KRAS G12 mutation are identified as having a specific molecular profile that responds well to the MEK/SRC inhibitor combination. This localized treatment strategy focuses therapeutic intensity on the appropriate patient population rather than applying uniform treatment to all patients.
Solution Approach 2:
The patent utilizes parameter changes by measuring SRC p419 expression levels and KRAS mutation status to stratify patients into different treatment groups. These molecular parameters serve as biomarkers that predict response to the combination therapy. By monitoring and selecting patients based on these specific parameters, the treatment efficacy is maximized while avoiding exposure to complex therapy in patients unlikely to benefit.
Data Source
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AI summary
A method of treating colorectal cancer (CRC) is provided. The method comprises administering to a subject in need thereof a therapeutically effective amount of a Mitogen/extracellular signal-regulated kinase (MEK) inhibitor and a SRC Proto-Oncogene, Non¬ Receptor Tyrosine Kinase (SRC) inhibitor, wherein cancer cells of the subject express an amount of SRC p419 above a predetermined level and do not express a KRAS G12 mutation, thereby treating the CRC.