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High-content multiplexed tissue imaging and quantification for cancer drug discovery
Beverly L Falcon1, Julie Stewart, Scharri Ezell
1Eli Lilly and Company, Department of Cancer Angiogenesis, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Abstract:
Targeting multiple hallmarks of cancer with drug combinations may provide unique opportunities for cancer therapeutics; however, phenotypic quantification is necessary to understand in vivo mechanisms of action of each drug alone or in combination. Immunohistochemistry (IHC) can quantify phenotypic changes, but traditional methods are not amenable for high-throughput drug discovery. In this article, we describe a high-content method to quantify changes in tumor angiogenesis, vascular normalization, hypoxia, tumor cell proliferation, and apoptosis using IHC. This method to quantify tumor model phenotypes can be useful for cancer drug discovery by increasing the understanding of: (i) tumor models used in efficacy studies, (ii) changes occurring during the growth of the tumor, and (iii) novel mechanisms of actions of cancer therapeutics.
Insights
This study introduces a high-content immunohistochemistry (IHC) method for quantifying tumor phenotypes. This approach aids cancer drug discovery by detailing drug effects on angiogenesis, hypoxia, proliferation, and apoptosis in vivo.
Area of Science:
- Oncology
- Cancer Therapeutics
- Drug Discovery
Background:
- Targeting multiple cancer hallmarks with drug combinations is a promising therapeutic strategy.
- Understanding the in vivo mechanisms of action for single agents and combinations requires phenotypic quantification.
- Traditional immunohistochemistry (IHC) methods are not suitable for high-throughput drug discovery.
Purpose of the Study:
- To develop a high-content IHC method for quantifying key tumor phenotypes.
- To enable a deeper understanding of cancer drug mechanisms of action.
- To facilitate high-throughput analysis in cancer drug discovery.
Main Methods:
- Development of a high-content method utilizing immunohistochemistry (IHC).
- Quantification of tumor angiogenesis, vascular normalization, hypoxia, tumor cell proliferation, and apoptosis.
- Application of the method to quantify phenotypic changes in tumor models.
Main Results:
- The described high-content IHC method allows for quantitative assessment of multiple tumor phenotypes.
- This method increases understanding of tumor models and their responses to therapeutic interventions.
- Novel mechanisms of action for cancer therapeutics can be elucidated.
Conclusions:
- A high-content IHC method provides a powerful tool for phenotypic quantification in cancer research.
- This approach is valuable for advancing high-throughput cancer drug discovery.
- Improved understanding of drug efficacy and mechanisms in vivo is achievable.
