ESR1 Mutation Detection for Hormone Therapy Resistance
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Solution Overview
Problem
There is a need for identifying novel genetic lesions associated with cancer, as existing technologies have limitations in effectively addressing cancer treatment resistance.
Innovation Solution
The discovery of novel mutations in the Estrogen Receptor 1 (ESR1) gene, specifically deletions and missense mutations in the ligand binding domain, hinge domain, and other regions, which can lead to altered ESR1 polypeptide activities and resistance to hormone therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional hormone therapies are used to treat estrogen receptor-positive cancers, then initial treatment response is achieved, but treatment resistance develops over time
Solution Approach 1:
The patent performs preliminary identification of ESR1 mutations (such as Y537S, Y537C, and hinge region mutations) before treatment resistance fully develops. By detecting these genetic lesions early through sequencing methods, clinicians can anticipate resistance mechanisms and adjust therapy proactively, maintaining treatment effectiveness throughout the disease course rather than waiting for failure to occur
Solution Approach 2:
The patent implements a feedback mechanism where ESR1 mutation status is continuously monitored in cancer cells during treatment. This feedback loop allows detection of acquired mutations (such as Y537 substitutions that confer tamoxifen resistance) and triggers therapeutic adjustments, creating a dynamic response system that adapts to changing tumor genetics to maintain long-term treatment efficacy
2Measurement precision
If existing genetic testing methods are used to identify cancer mutations, then known mutations are detected, but novel ESR1 mutations are missed
Solution Approach 1:
The patent employs universal sequencing methodologies that can detect all types of genetic lesions in the ESR1 gene simultaneously - including point mutations, insertions, deletions, and hinge region variants. This multi-functional approach replaces multiple specialized tests with a single comprehensive assay that identifies both previously known mutations and novel variants (such as the newly characterized Y537C and other hinge domain mutations), enhancing both precision and coverage
Solution Approach 2:
The patent performs preliminary comprehensive sequencing of the entire ESR1 coding region before treatment decisions are made. This upfront identification of all possible mutations (including rare variants like Y537S and hinge region deletions) ensures that no potential resistance mechanism is missed, allowing for more accurate treatment selection from the outset
Data Source
AI summary
Novel mutant ESR1 molecules and uses are disclosed.