Recent studies in advanced prostate cancer have identified emerging treatment targets and mechanisms of treatment resistance. At the 2017 European Society of Medical Oncology (ESMO) Annual Meeting, Dr. Himisha Beltran chaired and moderated a session evaluating the use of liquid biopsies – blood tests used to glean information about tumors – as a useful clinical tool for prostate cancer management.
While there are no formal guidelines on who, when, how and what to test for in prostate cancer, Dr. Beltran’s expertise provided important guidance to the global oncology community on this topic, as the prospect that a blood test might reveal many insights about the cancer and the tumor makeup has led oncologists to feel excited. Several steps are still needed for broad clinical implementation.
As tumors grow, some of their cells may enter into the bloodstream. These cells are known as circulating tumor cells (CTCs) and travel throughout the body along with fragments of tumor cell DNA known as circulating tumor DNA (ctDNA). Compared with traditional biopsies which extract tissue directly from the tumor, liquid biopsies offer a less invasive way for doctors to detect molecular biomarkers and learn more about what’s going on with someone’s cancer. Liquid biopsies can also better capture tumor heterogeneity, as CTCs and ctDNA can provide a window into the entire tumor (and metastatic sites), compared with a traditional biopsy in which typically only one part of the tumor is sampled. Thus, with a simple blood test, doctors can potentially access a more comprehensive view of an individual’s cancer, which can then help them determine the best treatment for that person. Blood testing can also be more easily repeated throughout the course of treatment in order to monitor disease changes in response to therapy, so liquid biopsy offers ways to detect treatment resistance and resistance mutations early on and throughout the course of the disease.
There is an emerging role for molecular testing in advanced prostate cancer since this information can better inform treatment decisions involving targeted therapies, such as PARP inhibitors, platinum-based chemotherapy, and immunotherapies. Liquid biopsies such as ctDNA may provide information about the genomic alterations present in the cancer, which can be used to help predict how people might respond to certain therapies.
Through liquid biopsies, physicians and researchers can also better detect signs of therapy resistance that may be emerging. For example, if a patient has a gene amplification or mutation detected in ctDNA that involves the androgen receptor (AR) gene, or AR splice variants expressed in CTCs, this may indicate that potent AR-targeted therapies may be less likely to work. This is because the cancer cells may develop various ways to reactivate androgen receptor signaling by acquiring extra copies of the AR gene (gene amplification), activating AR mutations, and/or AR splice variants (such as the AR-V7 variant), all of which result in downstream over-activity of the AR-pathway. Knowing this information up front may spare people from the side effects from a treatment likely to be ineffective. Current research is focused on developing more effective AR pathway inhibitors in this setting. CTCs may also identify other features of the cancer such as localization of the AR in response to taxanes as observed in the TAXYNERGY trial, tumor heterogeneity, and expression of emerging therapeutic targets.
Through a grant from the Prostate Cancer Foundation (PCF), Dr. Beltran and colleagues at WCM are working as part of an international consortium to develop, validate, and implement a ctDNA platform for prostate cancer. This targeted genomic sequencing test, called PCF SELECT, identifies tumor mutations in ctDNA from metastatic prostate cancer patients to guide treatment selection based on precision medicine. It is currently undergoing centralized development, and the long-term goal is that this ctDNA test will be widely used by the clinical prostate cancer community for precision medicine applications.
While liquid biopsies do have promise for these indications and can help guide decisions on the most appropriate treatments for prostate cancer patients, it is important that both patients and clinicians understand the advantages and limitations of available and emerging technologies. Undergoing treatment at a center of excellence that contributes to research on emerging trends allows individuals the opportunity to be among the first to access cutting-edge technologies that may benefit them.