Somatic Modeling of Estrogen-Receptor-Positive Breast Cancer in Rats

ASPIRE Award (2022-Present)

Jos Jonkers, PhD, Netherlands Cancer Institute, The Netherlands

Jos Jonkers, PhD

Breast cancer is the most common type of cancer in women, and more than 80% of breast cancers depend on hormone signaling for their proliferation. However, modeling hormone-dependent, estrogen-receptor positive (ER+) breast cancer in preclinical studies remains a major unmet need. While mice are a mainstay of preclinical cancer research, the development of genetically engineered mouse models of ER+ breast cancer has proven to be challenging. The vast majority of these models develop ER-negative mammary tumors, and the few models that do develop ER+ disease do not respond to estrogens or endocrine therapy, making them poor predictors for human clinical studies.

To overcome these challenges, Jos Jonkers and his lab have employed genetic engineering of the rat mammary gland to generate novel rat models of ER+ breast cancer. Now, they will expand on these findings by generating and using rat strains expressing Cas9 to enable somatic inactivation of tumor suppressor genes alone or in combination with oncogenes involved in ER+ breast cancer. The resulting platform of somatically engineered rat models will be used to study the origins of ER+ breast cancer, the immune response to it, and establish robust preclinical systems for in vivo drug efficacy studies.

published Research

Nicotra R, Lutz C, Messal HA, Jonkers J. Rat Models of Hormone Receptor-Positive Breast Cancer. J Mammary Gland Biol Neoplasia. 2024.