Tumor Microenvironment mTORC1 Testing for Clear-Cell RCC Resistance
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Solution Overview
Problem
Resistance to mTORC1 inhibitors develops during treatment of renal cell carcinoma, particularly clear-cell RCC, due to acquired resistance in tumor microenvironment cells rather than cancer cells, limiting the efficacy of existing therapies.
Innovation Solution
Identify mTORC1 inhibitor efficacy by contacting tumor microenvironment cells with the inhibitor and detecting mTOR inhibition, measuring phosphorylation levels or ATP hydrolysis to select appropriate treatment regimens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mTORC1 inhibitors are used to treat renal cell carcinoma, then initial treatment efficacy is achieved, but resistance develops during treatment limiting long-term efficacy
Solution Approach 1:
The patent applies preliminary action by assessing mTORC1 inhibition capability in tumor microenvironment cells before initiating treatment. This predictive assessment identifies patients whose microenvironment cells will remain inhibited by mTORC1 inhibitors, thereby predicting sustained treatment response and preventing early resistance development. The preliminary testing of tumor microenvironment cell responses to mTORC1 inhibitors guides treatment selection before therapy begins.
Solution Approach 2:
The patent implements feedback by monitoring mTORC1 inhibition status in tumor microenvironment cells during treatment. This involves periodically assessing whether microenvironment cells remain inhibited, providing real-time feedback on treatment effectiveness. Based on this feedback, treatment regimens are adjusted - continuing mTORC1 inhibitor therapy when inhibition is maintained, or switching to alternative treatments when resistance develops in the microenvironment.
2Duration of action of stationary object
If mTORC1 inhibitor therapy is continued long-term, then sustained treatment exposure is achieved, but acquired resistance in tumor microenvironment cells diminishes treatment efficacy
Solution Approach 1:
The patent uses feedback mechanisms to monitor mTORC1 inhibition status in tumor microenvironment cells during long-term treatment. Periodic assessments determine whether microenvironment cells remain inhibited or have developed resistance. This feedback enables dynamic adjustment of treatment duration - maintaining therapy when effective, and switching to alternative regimens when resistance emerges, thereby optimizing both treatment exposure and efficacy.
Solution Approach 2:
The patent applies dynamics by transitioning from static treatment protocols to dynamic, adaptive therapy. Treatment regimens are adjusted based on real-time assessment of microenvironment cell responses. This may involve changing mTORC1 inhibitor dosage, switching between different mTORC1 inhibitors, or alternating with other therapeutic approaches based on the current inhibition status of tumor microenvironment cells.
3Adaptability or versatility
If conventional kinase inhibitors are used, then broad activity is achieved, but lack of specificity limits targeted therapy benefit
Solution Approach 1:
The patent applies local quality by focusing mTORC1 inhibition specifically in tumor microenvironment cells rather than applying broad kinase inhibition systemically. The assessment and treatment are tailored to the specific characteristics of each patient's tumor microenvironment, evaluating which patients have microenvironment cells that respond to mTORC1 inhibition. This localized approach targets the specific cellular compartment (tumor microenvironment) that drives resistance, rather than applying uniform broad-spectrum inhibition.
Data Source
AI summary
Provided herein are methods for determining whether a subject is suitable for mTORC1 inhibitor treatments, as well as methods for determining whether an ongoing mTORC1 inhibitor treatment should continue.