Scientists at Weill Cornell Medicine have identified two new subtypes of prostate cancer. These new forms of the disease are resistant to usual treatments, but categorizing and studying them could lead to new therapies.
Most prostate cancers are fairly slow-growing, with a range of treatment options available. In some cases hormone therapy is administered, which reduces the levels of male hormones like testosterone that the cancer cells depend on to grow. However, some tumors can develop resistance to this treatment, becoming more deadly and harder to fight.
In the new study, the researchers found that there were four subtypes of this castration-resistant prostate cancer (CRPC), including two that had never been identified before. They named them SCL and WNT, after the signaling pathways that become overactive in each tumor type.
The team began by analyzing 40 tumor samples, grown as organoids from tumor cells collected from patients. They studied the DNA and RNA of the cells, as well as their chromatin, a mixture of DNA and proteins that tightly packages chromosomes in a cell. Differences in chromatin can make genes more or less available for expression, which can contribute to some types of cancer, so by analyzing chromatin profiles the team identified the four types of CRPC.
Next, the scientists calculated the proportion of each type within resistant prostate cancer cases, by sequencing the RNA of tumors from 366 patients. They found that the SCL type accounted for between 22 and 30 percent of cases, while WNT was much rarer, at just five to seven percent.
Looking deeper, the team was able to identify what was going wrong in SCL prostate cancers. A series of proteins – FOSL1, TEAD, YAP and TAZ – become too active, which changes chromatin accessibility and drives tumor growth. Having shed light on which proteins are involved, existing molecules that are known to affect them were then shown to slow the growth of SCL cancer cells, indicating new treatments could be possible.
“Once you can identify which type of tumor patients have, that’s very powerful information,” said Dr. Etka Khurana, co-senior author of the study. “For patients that fall into this SCL group, we have found very promising drug targets, which future studies will work to validate.”
The research was published in the journal Science.
Source: Weill Cornell Medicine
