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Updated: Mar 12, 2026
High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts
Published on: December 20, 2024
Steroid Hormone Receptor Positive Breast Cancer Patient-Derived Xenografts
Shawna B Matthews1, Carol A Sartorius2
1Department of Pathology, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave MS8104, Aurora, CO, 80045, USA.
Abstract:
The vast majority of breast cancers are positive for estrogen receptor (ER) and depend on estrogens for growth. These tumors are treated with a variety of ER-targeted endocrine therapies, although eventual resistance remains a major clinical problem. Other steroid hormone receptors such as progesterone receptor (PR) and androgen receptor (AR) are emerging as additional prospective targets in breast cancer. The fundamental mechanism of action of these steroid receptors in gene regulation has been defined mainly by several breast cancer cell lines that were established in the late 1970s. More recently, breast cancer patient-derived xenografts (PDX) have been developed by multiple groups at institutions in several countries. These new models capture the large degree of heterogeneity between patients and within tumors and promise to advance our understanding of steroid hormone receptor positive breast cancer and endocrine resistance. Unfortunately, steroid hormone receptor positive breast cancers are much more difficult than their receptor negative counterparts to establish into sustainable PDX. Herein we discuss the derivation of steroid hormone receptor positive breast cancer PDX, several pitfalls in their genesis, and their utility in preclinical and translational steroid hormone receptor research.
Insights
Estrogen receptor (ER) positive breast cancers are common but develop resistance to endocrine therapies. New patient-derived xenografts (PDX) models show promise for studying steroid hormone receptor research and resistance mechanisms.
Area of Science:
- Oncology
- Endocrinology
- Genetics
Background:
- Estrogen receptor (ER) positive breast cancers constitute the majority of cases and rely on estrogens for growth.
- Current ER-targeted endocrine therapies face challenges due to eventual treatment resistance.
- Progesterone receptor (PR) and androgen receptor (AR) are emerging as potential therapeutic targets in breast cancer.
Purpose of the Study:
- To discuss the derivation of steroid hormone receptor positive breast cancer patient-derived xenografts (PDX).
- To highlight pitfalls encountered during the genesis of these models.
- To explore the utility of PDX models in preclinical and translational steroid hormone receptor research.
Main Methods:
- Utilizing established breast cancer cell lines for fundamental mechanism studies.
- Developing and characterizing patient-derived xenografts (PDX) from breast cancer patients.
- Comparing the derivation success rates between steroid hormone receptor positive and negative breast cancers in PDX models.
Main Results:
- Patient-derived xenografts (PDX) capture significant inter- and intra-tumoral heterogeneity.
- Steroid hormone receptor positive breast cancers present greater challenges in establishing sustainable PDX compared to receptor-negative counterparts.
- PDX models offer a promising avenue for advancing research into steroid hormone receptor positive breast cancer and endocrine resistance.
Conclusions:
- Steroid hormone receptor positive breast cancer PDX models are crucial for understanding treatment resistance.
- Overcoming challenges in PDX derivation is key to unlocking their full translational potential.
- These advanced models will facilitate the development of novel therapeutic strategies for endocrine-resistant breast cancer.
