July 12, 2024
Hokkaido University
University of the Ryukyus
Keio University
Key Points
Successfully created a drug-resistant model of extramammary Paget's disease, a skin cancer that commonly affects the vulvar region in the elderly.
Elucidated the drug resistance mechanism in extramammary Paget's disease.
Expected to advance the development of anticancer drugs for extramammary Paget's disease.
A research group led by Visiting Researcher Teruki Yanagi (currently Associate Professor at the Graduate School of Medicine, University of the Ryukyus) and Professor Hideyuki Ujiie of the Graduate School of Medical Sciences, Hokkaido University, and Associate Professor Takeru Funakoshi and Professor Hiroshi Nishihara of the Keio University School of Medicine, has established a drug-resistant model of extramammary Paget's disease.
Extramammary Paget's disease is a type of skin cancer that tends to develop in the vulvar region of the elderly, and the number of patients is increasing with the aging population. Although several anticancer drugs have been developed for extramammary Paget's disease, a problem has been that their effectiveness can diminish over time (i.e., drug resistance).
The research group therefore used a mouse model of extramammary Paget's disease to establish a model of resistance to the drug trastuzumab. A comparison of genetic mutations in tumor tissue before and after acquiring drug resistance revealed the loss of a gene called PTEN. This genetic change has also been observed in trastuzumab-resistant breast cancer. Furthermore, when several drugs were administered to these trastuzumab-resistant tumors, multiple effective agents that reduced tumor size were found.
This new drug-resistant skin cancer model is expected to be useful for future elucidation of the pathology of extramammary Paget's disease and the development of new therapies.
The results of this research were published online in the *British Journal of Cancer* on July 10, 2024.
Please see below for the full press release.