When bacteria develop antibiotic resistance, treatment with these medications becomes ineffective. Similarly, tumor cells can also change in such a way that renders them resistant to particular medications. This makes it vitally important for cancer patients and their doctors to determine as early as possible whether a specific therapy is working or not.
A new blood test developed by researchers at the Technical University of Munich (TUM) can predict drug resistance in patients with advanced prostate cancer.
Prostate cancer tumour cells require the androgen hormone, testosterone, to grow. They possess a receptor to which testosterone binds and then signals the cancer cells to divide and grow. If a prostate tumour has already grown to a large size and started spreading throughout the body, therapeutic drugs are used to block growth where it starts – either by targeting tumour cell receptors to prevent testosterone from binding, or they entirely block the body’s overall production of testosterone. Two of the drugs most frequently used in this type of therapy are abiraterone and enzalutamide.
During the course of treatment, however, some tumour cells develop resistance to these drugs, and continue to grow and metastasize. The culprit: the tumour’s testosterone receptors have changed their structure, and the new variant can signal cancer cells to continue dividing and spreading – even without testosterone. The most common receptor variant seen in patients is called AR-V7.
‘If we know in advance whether or not a tumour has developed cells with this receptor, we can provide advice on an individual basis at an early stage – this can spare seriously-ill patients from undergoing an ineffective therapy,’ explained Assistant Professor, Dr Matthias Heck, co-leader of the study and a specialist for Urology at the University Hospital TUM Klinikum rechts der Isar in Munich.
Heck and his team collaborated with colleagues led by Dr Christof Winter, a physician and bioinformatician and the head of the Liquid Profiling and Bioinformatics lab at the TUM Institute of Clinical Chemistry and Pathobiochemistry to develop a new blood test.
Until now, blood tests used to detect prostate tumour cells have looked for specific surface structures on the cells. It’s not only a time-consuming and expensive process because of the special equipment required for the tests, but it’s also not always efficacious. If the cells being tested lack the specific structure being searched for, these tests fail to detect their presence.
The new test developed by TUM researchers utilises a completely different method for looking at different markers in order to reliably, quickly and inexpensively measure the presence of the modified receptor AR-V7 at an early stage. Moreover, it can also determine whether or not the tumor is resistant to treatment with abiraterone and enzalutamide.
The new blood test provides an alternative to and has the potential to improve existing testing methods: It analyses the amount of AR-V7 RNA molecules in the blood. In each and every one of the cells in our body, RNA is responsible for the translation of genetic information into protein molecules, including receptor molecules. If the test detects high levels of AR-V7 RNA in the blood, it’s evidence that the patient has already developed tumor cells resistant to therapy with abiraterone and enzalutamide.