Significance

Although men with prostate cancer usually respond to standard treatment with hormone therapy or chemotherapy, many will eventually experience progression or recurrence despite treatment—particularly those with high-risk or aggressive forms of the disease. In preclinical laboratory research, a team led by Dean Tang, Ph.D., Chair of Pharmacology and Therapeutics at Roswell Park Cancer Institute has discovered a unique population of normal stem cells that are intrinsically resistant to conventional treatments and may enable prostate cancer relapse. In a new publication in the journal Stem Cell Reports, the team reports its development of a novel preclinical model that allows not only the labeling but also the purification of this rare but persistent population of prostate stem cells, which are dormant and, strikingly, resemble high-risk prostate cancer at the molecular level.

The normal prostate and most prostate tumors contain a small number of cells called luminal progenitors that, unlike the bulk of cancer cells, are generally dormant. They behave like stem cells, lacking expression of the molecules targeted by current cancer treatments. As a result, these cells evade prostate cancer treatments such as chemotherapy and radiation, which generally target and eliminate cells that are rapidly multiplying and dividing. Unlike most prostate cancer cells, these dormant, stem-like cells are also less dependent on androgens, making them relatively unresponsive to chemical castration or hormone therapy, approaches designed to “starve” tumors by depriving them of their androgen fuel.

“The existence of a population of quiescent or slow-cycling cells in the prostate has been suggested, but their identity and characteristics were unknown because they are rare and very difficult to study,” explains Dingxiao Zhang, Ph.D., an Assistant Professor with the Department of Pharmacology and Therapeutics at Roswell Park and first author on the new study. “We were able to identify a unique population of cells that might serve as the origin of treatment-resistant prostate cancer. Our genetic model paves the way toward the next step, which is the development of therapies that can target these dormant cancer cells, which are expected to significantly improve the treatment of prostate cancer and delay or even prevent its recurrence.”

 

 

 

Dingxiao Zhang

Dingxiao Zhang

Ph.D., an Assistant Professor with the Department of Pharmacology and Therapeutics at Roswell Park.

Dr. Zhang joined the RPCI faculty in 2016. He graduated from Chungbuk National University with a PhD degree in Molecular Embryology from one of the National research laboratories in South Korea. During his doctoral studies, he worked extensively on early embryo development and regulation of maternal gene expression, which led to 8 important publications (4 of which were first author papers) in the field. After finishing Ph.D studies, he did a short post-doctoral training at the University of Cincinnati College of Medicine, studying the role of MED1 and ARGLU1 in breast cancer, with a first author J. Biol. Chem. paper. He then joined MD Anderson Cancer Center as a postdoctoral fellow in February 2012. During his postdoctoral training at MDACC, he has published 8 papers (4 of which were first author papers). He was appointed to an Instructor position in 2015, and an Assistant Professor of Oncology in 2016. Currently, he is using genetic mouse models, cancer cell lines and xenografts, as well as human primary tumor samples to investigate the prostate development (epithelial biology) and prostate tumorigenesis and progression.