To determine the proportion of cases they each may comprise, the researchers used RNA sequencing data to classify 100 patients from Weill Cornell Medicine and 266 from the organization Stand Up to Cancer. The chromatin data led them to identify the four groups, including SCL and WNT. Changes in this packaging contribute to cancer by altering genes’ availability for expression. The researchers analysed these cells’ DNA, RNA, and how compactly their DNA was packaged, a characteristic known as chromatin accessibility.
Most of these came from a collection of organoids, which are tiny organ-like structures grown from tumour cells collected from patients at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center. For this study, however, the team had access to 40 tumour samples.
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Scientists seeking to investigate castration-resistant prostate cancer have generally lacked enough cells derived from patients to capture its full diversity. The new study identified two additional types of this disease: SCL and WNT, named for the signalling pathways that is overactive in tumours of these types. Others, meanwhile, shed their dependence on androgens and take on an aggressive form known as neuroendocrine. Some tumours may manage to resist the treatment, but still need testosterone and other hormones, which are called androgens collectively, to grow. Researchers already knew that this type of cancer encompasses more than one disease. “For patients that fall into this SCL group, we have found very promising drug targets, which future studies will work to validate,” said Dr Khurana. Studies have shown that this same molecular pathway drives other solid tumours, including colorectal cancer and malignancies of the breast and lung, so scientists are already working to develop ways of interfering with their activity. Within SCL tumour cells, they identified a set of proteins that work together to fuel this treatment-resistant disease. One of these, which they call stem cell-like (SCL), accounts for approximately a quarter of castration-resistant prostate cancers, she and her collaborators estimated.
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