DCIS Cell Models for Rapid Therapeutic Screening

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Solution Overview

Problem

Current therapies for premalignant breast lesions like DCIS lack understanding of molecular origins and are inefficient in assessing therapeutic efficacy due to long waiting times for recurrence, necessitating a novel therapeutic target and rapid assessment method.

Innovation Solution

Development of isolated human breast ductal carcinoma in situ (DCIS) cell populations that form 3-D spheroids, expressing specific markers, and are inhibited by chloroquine, allowing for in vitro and in vivo testing of therapeutic agents to inhibit growth and invasion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional therapies are used for DCIS, then treatment is provided, but therapeutic efficacy cannot be rapidly assessed due to long waiting times

Engineering Contradiction:
Improvetherapeutic efficacy assessmentVSAvoidwaiting time for recurrence
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent creates in vitro models (cell cultures and organoids) that copy DCIS tissue architecture and behavior. These models allow rapid testing of therapeutic agents without requiring years of clinical follow-up, as the in vitro systems can assess treatment effects on cell proliferation, invasion, and survival within days or weeks rather than years.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent establishes pre-clinical in vitro assessment systems that perform preliminary evaluation of therapeutic agents before clinical deployment. By using DCIS cell cultures and organoids to screen treatments in advance, the system identifies effective therapies rapidly without requiring long-term patient follow-up to assess efficacy.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If new therapies are developed for DCIS, then treatment options are improved, but molecular origin understanding is limited

Engineering Contradiction:
Improvetherapy optionsVSAvoidmolecular origin knowledge
Core Design Contradiction:
Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent uses in vitro DCIS models as intermediary systems between basic molecular research and clinical therapy. These models preserve molecular characteristics of DCIS while allowing controlled manipulation and observation, enabling researchers to study molecular mechanisms and test therapies without the complexity and ethical constraints of clinical trials.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If autophagy inhibitors are used to treat DCIS, then cell growth is inhibited, but potential toxicity must be managed

Engineering Contradiction:
ImproveDCIS cell growth inhibitionVSAvoidtherapy toxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs autophagy inhibitors at controlled concentrations in in vitro models to achieve sufficient DCIS cell growth inhibition while maintaining manageable toxicity levels. By testing partial doses in the controlled in vitro environment, the system can optimize therapeutic windows before clinical application.

Inventive Principle:
Principle #16Partial or excessive action

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 rapid evaluation of therapeutic agents and potential treatments for pre-neoplastic breast lesions by inhibiting DCIS cell growth and invasion, providing a novel therapeutic target for premalignant breast cancer.

Implementation Method 1

the cells... are inhibited in formation of 3-D structures and migration by treatment with chloroquine

Methodology Applied
Scientific EffectAutophagy inhibition:

Data Source

PatentUS9096833B2Methods of treating pre-malignant ductal cancer with autophagy inhibitors
Publication Date: 2015.08.04 GEORGE MASON UNIVERSITY
  • US9096833B2 patent drawing
  • US9096833B2 patent drawing
  • US9096833B2 patent drawing

AI summary

Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine. In one embodiment, there is a loss of heterozygosity (LOH) that is narrowly confined to a region of chromosome 6p (6p21.1-6p12.3) that contains the SUPT3H gene.