SASH1 Expression Biomarker for PARP Inhibitor Sensitivity
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Solution Overview
Problem
Current therapeutic strategies for breast cancer and other cancers lack effective biomarkers for predicting responsiveness to PARP inhibitors, leading to the need for large clinical trials and limited treatment options for triple-negative breast cancer and other solid tumors.
Innovation Solution
Determining the expression levels of the SASH1 protein or nucleic acid in cancer cells to predict responsiveness to PARP inhibitors, with decreased SASH1 levels indicating increased responsiveness and increased levels indicating decreased responsiveness, allowing for personalized treatment approaches.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BRCA1/2 mutation status is used as a biomarker for PARP inhibitor sensitivity, then treatment targeting can be established, but the biomarker reliability is insufficient leading to large Phase III clinical trials being required
Solution Approach 1:
The patent shifts from using BRCA1/2 mutation status as the biomarker parameter to using SASH1 expression levels (mRNA or protein) as the predictive parameter. This parameter change provides more reliable prediction of PARP inhibitor sensitivity, thereby reducing the need for large Phase III clinical trials to demonstrate survival benefit.
Solution Approach 2:
The patent replaces the genetic mutation detection approach (BRCA1/2 status) with an expression level measurement approach (SASH1 mRNA or protein levels). This substitution provides a more sensitive and reliable biomarker that can predict PARP inhibitor response without requiring extensive clinical trial validation.
2Adaptability or versatility
If current therapeutic strategies based on hormone receptor and HER2 status are used, then treatment options are established for receptor-positive cancers, but treatment options are most limited for triple-negative tumours
Solution Approach 1:
The patent makes the SASH1 biomarker universally applicable across multiple cancer types including breast cancer, lung cancer, and other solid tumors. Unlike hormone receptor status which only guides treatment for specific subtypes, SASH1 expression levels can predict PARP inhibitor sensitivity across diverse cancer types, particularly providing value for triple-negative breast cancer where treatment options are limited.
3Ease of operation
If SASH1 expression levels are determined as a predictive biomarker, then personalized treatment approaches can be implemented, but additional diagnostic testing is required
Solution Approach 1:
The patent segments the diagnostic process into a specific SASH1 expression level determination step that can be performed using established molecular biology techniques. This segmentation allows the biomarker assessment to be integrated into existing diagnostic workflows without requiring entirely new complex testing infrastructure.
Data Source
AI summary
Provided herein are methods of treating a cancer with or predicting the responsiveness of a cancer to an anti-cancer agent which is capable of inhibiting an enzyme that mediates repair of DNA strand breaks, such as PARP, said method including the step of determining an expression level of SASH1. A method of treating a cancer that includes administering a therapeutically effective amount of an agent that increases the expression and/or an activity of SASH1 is also provided. Further provided herein are methods for identifying an agent that modulates the expression and/or an activity of SASH1 for use in the treatment of cancer.