Labeled HSP90 Inhibitors for Non-Invasive Tumor Response Prediction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current HSP90 inhibitor therapies lack effective biomarkers for patient selection, invasive assays for pharmacodynamic monitoring, and inadequate understanding of optimal dosing and scheduling, leading to ineffective treatments and potential toxicity without clinical benefit.
Innovation Solution
Development of non-invasive assays using labeled HSP90 inhibitors, such as fluorescently labeled and radiolabeled PU-H71, to measure the abundance of 'oncogenic HSP90' in tumors, predicting sensitivity to HSP90 inhibition therapy and optimizing dosing through PET imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If plasma pharmacokinetics are used to guide HSP90 therapy, then treatment can be administered systemically, but tumor-specific drug concentrations cannot be accurately predicted leading to potential toxicity and inefficacy
Solution Approach 1:
The patent uses radiolabeled HSP90 inhibitors as intermediaries to bridge the gap between systemic administration and tumor-specific measurement. The labeled inhibitors serve as tracers that accumulate in tumors and can be detected by PET imaging, allowing prediction of tumor drug concentrations without direct tissue sampling. This intermediary approach enables accurate measurement while maintaining the ease of systemic administration.
Solution Approach 2:
The patent replaces invasive mechanical biopsy procedures with non-invasive PET imaging. Instead of mechanically extracting tumor tissue for pharmacokinetic analysis, the system uses radiolabeled inhibitors that can be detected through imaging, substituting a minimally invasive measurement approach while maintaining the ability to quantify tumor-specific drug concentrations.
2Productivity
If HSP90 inhibitors are administered to cancer patients, then anti-tumor activity can be achieved, but patient selection remains unclear leading to ineffective treatment for many patients
Solution Approach 1:
The patent implements feedback by using PET imaging with radiolabeled HSP90 inhibitors to measure tumor-specific drug concentrations and HSP90 inhibition levels in patients. This feedback information can be used to predict which patients are most likely to respond to HSP90 therapy, allowing for better patient selection and personalized treatment strategies before full treatment begins.
Solution Approach 2:
The patent enables preliminary assessment of patient suitability for HSP90 therapy by measuring radiolabeled inhibitor uptake in tumors before initiating treatment. This preliminary imaging can identify patients with high HSP90 expression and appropriate tumor characteristics, allowing for pre-treatment stratification and selection of the most likely responders.
3Measurement precision
If invasive biopsy assays are used to measure HSP90 inhibition, then direct tumor measurement is possible, but logistical and ethical issues limit their use
Solution Approach 1:
The patent substitutes invasive mechanical biopsy procedures with non-invasive PET imaging technology. Radiolabeled HSP90 inhibitors can be administered systemically and their tumor accumulation can be visualized and quantified through PET scans, eliminating the need for tissue extraction while maintaining measurement precision of HSP90 inhibition in the tumor microenvironment.
Solution Approach 2:
The patent introduces radiolabeled HSP90 inhibitors as intermediary tracers that mediate between the therapeutic agent and the measurement system. These labeled inhibitors accumulate in tumors and serve as detectable signals that reflect HSP90 inhibition levels, allowing indirect but accurate measurement without requiring direct tissue access.
4Quantity of substance
If HSP90 inhibitors are given at high doses to ensure tumor penetration, then effective concentrations can be achieved, but plasma toxicity increases
Solution Approach 1:
The patent uses PET imaging with radiolabeled HSP90 inhibitors to provide real-time feedback on tumor-specific drug concentrations and distribution. This feedback allows clinicians to optimize dosing regimens by identifying the minimum effective dose that achieves adequate tumor penetration without causing excessive plasma toxicity, enabling personalized dose adjustment for each patient.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables personalized treatment by identifying responsive patient populations and determining effective tumor drug concentrations, reducing unnecessary exposure and toxicity.
Implementation Method 1
The invention also provides radiolabeled inhibitors that selectively identify and interact with this tumor 'oncogenic HSP90' species, making it feasible to measure the abundance of the 'oncogenic HSP90' species in different types of tumors
Implementation Method 2
Different fluorescently labeled and ANCA-labeled versions of the HSP90 inhibitor PU-H71 are provided that have been optimized for use in flow cytometry and for the analysis of cancer cells
Implementation Method 3
contacting the tumor or a sample containing cells from the tumor with a detectably labeled HSP90 inhibitor which binds preferentially to a tumor-specific form of HSP90 present in a tumor or tumor cells
Data Source
AI summary
This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.