A new and very prevalent kind of prostate cancer
A recent study by a group of researchers at Memorial Sloan Kettering Cancer Center (MSK) and Weill Cornell Medicine finds that a previously unidentified subtype of hormone-resistant prostate cancer makes up roughly 30% of all cases. The study was recently published in the journal Science. The discovery could make it possible for patients with this subtype of prostate cancer to get targeted therapies.
Only two prostate cancer subtypes had previously been identified: androgen-dependent and neuroendocrine before this recent research, which was led by Yu Chen. Dr. Chen is an MSK physician-scientist, a member of the Human Oncology and Pathogenesis Program, and an associate professor at Cornell. Because some of the genes that are switched on in the cells are similar to those in stem cells, Dr. Chen’s team has termed the newly identified third subtype of prostate cancer stem cell-like (SCL).
Dr. Chen and his colleagues looked at 40 distinct patient-derived models of prostate cancer that were gathered from patients who had cancer treatment at MSK and Weill Cornell to make their discovery.
“We didn’t know whether we were going to find additional subtypes,” Dr. Chen says. “This is a field that’s been studied for many years, by many investigators. So we were happy and surprised to find that there’s this fairly large group of patients with tumors that haven’t been characterized.”
New insights are enabled by innovative technologies
The lack of sufficient high-quality laboratory models for researching this form of cancer may be one reason why the subtype eluded researchers.
“Prostate cancer is uniquely difficult to propagate in the lab,” Dr. Chen explains. “Whereas there are hundreds of cell lines of melanoma and lung cancer, there’s only three or four prostate cancer cell lines that are useful.”
To circumvent this problem, the team turned to a new technology called organoids. The organ-like structures are grown in the lab from pieces of a patient’s tumor. They are a kind of “avatar” of a patient’s tumor and can be used to study its genetics and biochemistry.
In addition, the team made use of patient-derived xenografts — tumors removed from a patient and grown in a mouse — for a total of 40 different patient-derived models of prostate cancer.
They could then determine whether genes are activated or inactive in the cells using these patient-derived organoids as a starting point. The scientists utilized this data to establish the existence of a new subtype of prostate cancer.
Next, they looked to see if the SCL subtype was apparent in a biobank of 366 prostate cancer tumors. It was. In fact, it was the second most prevalent group, after the androgen-sensitive type.
Knowing the molecular drivers of this common subtype of prostate cancer opens the door to approaches that could target these drivers with drugs.
Allowing for new treatment options
“For the past 80 years, the backbone of treatment for prostate cancer has been hormone-deprivation therapy,” Dr. Chen explains. “That’s because essentially all prostate cancers when they are first diagnosed, depend on testosterone signaling.”
“Once patients become resistant to antigen deprivation,” he continues, “it becomes a universally lethal disease.”
This is where the new findings could help improve treatment options. The scientists found that there are experimental drugs currently being tested in humans that can block the growth of the SCL subtype in laboratory and animal models. They are currently working with several companies to establish a clinical trial of their drugs for people with this subtype of prostate cancer.
The study was funded by the National Institutes of Health (grants P30CA008748, P50CA221745, P50CA211024, R37CA241486, R37CA241486-02, U54CA224079, U01CA224044, R01CA193837, R01CA208100, U01CA252048, R01CA228216, DP2CA174499, and R01CA218668); the Department of Defense (W81XWH-17-1-0653), Prostate Cancer Foundation; STARR Cancer Consortium; Geoffrey Beene Cancer Research Center; Irma T. Hirschl Trust; and WorldQuant Foundation. Dr. Chen holds interest and receives royalties from ORIC Pharmaceuticals.
Reference: “Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets” by Fanying Tang, Duo Xu, Shangqian Wang, Chen Khuan Wong, Alexander Martinez-Fundichely, Cindy J. Lee, Sandra Cohen, Jane Park, Corinne E. Hill, Kenneth Eng, Rohan Bareja, Teng Han, Eric Minwei Liu, Ann Palladino, Wei Di, Dong Gao, Wassim Abida, Shaham Beg, Loredana Puca, Maximiliano Meneses, Elisa de Stanchina, Michael F. Berger, Anuradha Gopalan, Lukas E. Dow, Juan Miguel Mosquera, Himisha Beltran, Cora N. Sternberg, Ping Chi, Howard I. Scher, Andrea Sboner, Yu Chen and Ekta Khurana, 27 May 2022, Science.