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Dr. Beltran is an Assistant Professor at Weill Cornell Medical College and specializes in Genitourinary Cancer.
Many men with metastatic prostate cancer develop castration-resistant prostate cancer (CRPC). This means that the cancer is able to grow and continue to spread despite being treated with hormone therapy. For men with CRPC, more treatment is needed to help control the growth of the cancer. To help these patients, doctors are studying CRPC at the molecular level. By finding genetic changes, or mutations, and using molecular prognosis and imaging technology, doctors hope to improve the treatment options for these patients. Prognosis is the chance of recovery.
Identifying Genetic Changes in CRPC
Researchers have mapped the genomic landscape of CRPC by using the molecular data of tumors from large groups of patients with localized and advanced prostate cancer. This is important because it tells researchers when genetic changes, like ERG gene rearrangements, SPOP mutations, and AR point mutations, occur during a patient’s cancer and treatment cycle. Doctors are using this knowledge to develop new treatments and to test current treatments.
We can detect specific features of a tumor for many patients with growing metastatic CRPC. These features provide information on tumor behavior. With this information, doctors can start to design treatments to specifically target the alterations in patients’ tumors. Targeting the genetic changes in the tumor may stop it from growing and spreading.
For example, when patients have metastatic CRPC that has a genetic change called AR-V7, current treatment strategies that target the AR gene do not work well. Based on this finding, new drugs are being developed to target the AR-V7 change. Recently, the U.S. Food and Drug Administration (FDA) sped up the review process for the drug olaparib (Lynparza), which is used as a treatment for patients with metastatic CRPC with BRCA1/2 or ATM mutations. Patients with those mutations who received this drug lived longer, compared with patients who received the drug but didn’t have those mutations. What remains unclear is why some, but not all, tumors have genetic changes and when they occur during treatment.
Improving Prognosis and Treatment at the Molecular Level
Metastatic biopsies are not usually done in cases of CRPC and advanced prostate cancer. These biopsies can be difficult to perform and may not always provide a complete picture. For these reasons, it is important to develop additional tools, including noninvasive methods, to identify molecular changes in the tumor that may help predict the course of the disease and determine which treatment to use. There are 3 methods in development:
- Circulating tumor DNA
- Circulating tumor cells
- Molecular imaging
Researchers can use advanced DNA sequencing to examine a patient’s blood for genetic changes that come from the tumor. This blood test is a noninvasive way of finding circulating tumor cells in patients with CRPC. Studies in prostate cancer have suggested that changes in circulating tumor DNA levels are linked with how well treatment works. This test can detect mutations that are found in metastatic tumors. These circulating tumor cells can also be used for molecular testing to look for specific alterations, such as AR-V7.
Advances in imaging technology can also help advance progress in drug development and personalized treatment. Molecular imaging can show where cancer has spread. It has the potential to find how far a disease has spread sooner than standard imaging technologies. However, it is not always clear how this information can best help patients. Ultimately, molecular imaging could be used in a number of ways, including as an early drug development tool, to identify biomarkers of a patient’s reaction to treatments, to see differences between areas of metastatic disease, and as an early sign that treatment is working.
Molecular-based tools used to examine genetic changes in prostate cancer offer a lot of potential for patients. Oncologists can now look at CRPC at the molecular level and may be able to more accurately assess if a treatment is working, determine staging and early detection of disease, and advance drug development. Although it is exciting, we still need more studies to learn how and when to best use these tools to improve patients’ lives and quality of life.