Update: 09 October 2021 23:23 STI
Washington [US], Oct. 9 (ANI): Researchers at the Medical College of Wisconsin Cancer Center and an international team of collaborators recently unblocked drug testing for hormone-sensitive human breast cancer using a mouse model.
The results of the study were published in the journal Science Advances, following the teams’ collaborative project on generating mice with an improved hormonal profile that supports the growth and metastatic spread of implanted human breast tumors.
The majority of breast cancer deaths are caused by estrogen receptor (ER) positive tumors. It is a long-standing challenge to develop untreated ER-positive breast tumors from patients in mice. The dearth of such models of human breast tumors has hampered efforts to identify better drugs or combinations of drugs. More effective treatments are needed to prevent the frequent development of resistance to current therapies and thus reduce breast cancer mortality.
ER-positive breast tumors are sensitive to the hormone prolactin, the best known to promote milk production in mothers. The researchers had previously found that mouse prolactin failed to activate human prolactin receptors and speculated that this hormonal deficiency was the key to the poor growth of ER-positive human breast cancer in mice.
This new study reports that by modifying the mouse prolactin gene, the team generated a breed of mice that produced blood levels of human prolactin similar to levels detected in patients. This new mouse model, called NSG-Pro, supports significantly improved growth of implanted ER-positive human breast cancers. Analyzes of tumor molecular pathways have revealed that prolactin works together with estrogen and Her2, two well-established growth factors for breast cancer.
The team has now generated a panel of estrogen-dependent transplantable breast tumor models from patients in NSG-Pro mice. Several of the new tumor lines recapitulate disease progression in patients by spreading to distant organs when implanted in the mammary glands of NSG-Pro mice. The research appears in the Sept. 15 online issue of the journal Science Advances.
“We are particularly excited about the opportunity to study distant metastases and test the efficacy of drugs on advanced ER-positive breast cancer, because until now such experimental models were not available. not available, âsaid Hallgeir Rui, WBCS Full Professor of Breast Cancer Research; director of MCW Tissue Bank; and professor and vice-president of pathology research at MCW. “This is especially important because breast cancer patients die from distant metastases.”
Oddly, after surgically removing primary tumors from the mouse mammary glands, the team documented that two different prolactin blocking treatments inhibited the growth of cancer cells that had spread to the lungs. Although more studies are needed, the results suggest that drugs targeting prolactin may be beneficial for some patients with ER-positive metastatic breast cancer.
“The NSG-Pro mouse model provides precision medicine approaches previously unavailable for ER-positive human breast cancers,” said Yunguang Sun, MD, PhD, study co-author and assistant professor of pathology and laboratory medicine at MCW. (ANI)