They discovered this by mapping how genes in the tumor cell are regulated, the so-called epigenetics. In the future, this three-way split may have implications for the way in which individual patients can best be treated.
A publication about this research was published on 21 November in the Nature Communications journal, with researcher Suzan Stelloo as the first author.
Wilbert Zwart: "We have known for almost 20 years that so-called subtypes exist for breast cancer: different types of breast cancer that are biologically different and also need to be treated differently. In prostate cancer, despite many years of intensive research, these subtypes were never really found."
Worldwide, one million men a year are diagnosed with prostate cancer and in the Netherlands there are 10,000. In about 75% of men with primary prostate cancer, surgery or radiation results in the permanent removal of the cancer. However, the cancer returns in a quarter of patients. At present, prostate cancer patients are often treated in the same way and 'tailor-made treatment' is not yet available to everyone at an early stage of the disease. Until now, in prostate cancer it has mainly been a matter of trial and error, says internist oncologist André Bergman, who is Zwart's permanent researcher partner. The division into three subtypes may change this.
Prostate cancer is a 'hormonal tumor', which means that this type of cancer depends on hormones to grow. The most important hormone in prostate cancer is testosterone. Testosterone binds to a protein in the tumor cell, the androgen receptor, allowing the tumor to grow. From previous research, the researchers already knew that the androgen receptor binds to very specific spots on the DNA of the tumor cell and that very specific DNA patterns (a kind of DNA fingerprint) enable us to predict in which patients prostate cancer may return those where it will not. This discovery is still in the 'scientific phase', but the group has recently received a grant from the Oncode Institute to further develop this test, hopefully into a clinical trial.
In the past, the search for subtypes of prostate cancer was mainly focused on DNA analyses or on analyses of gene activity (RNA analyses). Zwart: 'Over the past few years, our team has further developed new techniques that enable us to map the epigenetics in tumors - i.e. how genes in tumors are regulated - with extremely high sensitivity. We have now discovered that, when we combine all this data, we can distinguish between three different types of prostate cancer.
The third group: hormones appear less important
Now the researchers have discovered three different types of prostate cancer with their epigenetics experiments. The first two groups had already been found in previous research. However, the third group was a big surprise. All three of the subtypes found have the androgen receptor in the tumor cell, as is known in prostate cancer. In the third group, however, the DNA binding of the androgen receptor is greatly reduced, which would mean that these tumors would also be less sensitive to hormones. However, the tumor still grows. Zwart: Hormonal therapy may also be less successful in these patients. So the big question is: if the androgen receptor is not the main cause of this tumor growing, what factors is the tumor cell dependent on? We have done further research into this matter and found a number of possible weaknesses of this subgroup. Future clinical studies will aim to use this knowledge to help bring us closer to personalised treatment.
Stelloo et al., ' Integrative epigenetic taxonomy of primary prostate cancer', Nature Communications 21 November 2018 DOI: 10.1038/s41467-018-07270-2
This work has been made possible by subsidies from KWF, Oncode Institute, Alpe D'HuZes, ZonMW and Movember.