Prostate Cancer Lab #23: Liquid Biopsies (Peter Kuhn and Stephanie Shishido)

Peter Kuhn, PhD, Dean’s Professor of Biological Sciences and Professor of Medicine, Biomedical Engineering, Aerospace & Mechanical Engineering, and Urology, University of Southern California; Founder and Chief Scientific Advisor, Epic Sciences; and Stephanie Shishido, PhD, Director of Clinical Research, CSI-Cancer, University of Southern California, led a discussion on the cutting edge of liquid biopsies and their ability to inform patients about their disease (“Do I have cancer?”), predict progress (“How bad is the diagnosis?”), guide treatment decisions, (“Active surveillance vs. prostatectomy?”, “Will my treatment work?”), and monitor progress (“Is my treatment working?). 

Liquid biopsies hold out the promise of less invasive, lower cost, and more frequent capture of data about cancer and its environment, which could revolutionize treatment.

• How does liquid biopsy technology work?
  Liquid biopsies refer to collection of bodily fluids for analysis, usually blood draws, but can be of any fluid, including bone marrow aspirates. The analysis can look for “circulating tumor cells” (CTCs), which are cancer cells that split away from the primary tumor and enter the circulatory system (metastasis); or “cell-free DNA”, fragments of DNA released into the bloodstream when cells die. The DNA signature of healthy cells is very different from cancer cells, called “circulating tumor DNA” (ctDNA).
  
  
• What can patients learn from a liquid biopsy, especially prostate cancer patients who are already getting blood draws to monitor their PSA biomarker?
  We tend to focus on the tumor cells, but there’s a lot of information in the environment around the tumor cells we can get from liquid biopsies that can help us understand the tumor and its dynamics. For example, a blood test can tell if a patient has an androgen receptor variant (AR-V7), indicating that he will not respond to androgen-targeted therapies (such as abiraterone, enzalutamide, or apalutamide).
  
  
• How close is the promise of this new technology to widespread access?
  This technology is in an early research phase that seems like “The Wild West”. We don’t have clarity on which types of these liquid biopsies are relevant for which types of tumors at which stage in their progression. It’s hard to find practitioners who are nimble and are willing to do serial liquid biopsies so we can be addressing genetic changes along the way. It’s often hard to get these and other tests done, and they can be expensive.
  
  
• What’s next?
  In prostate cancer and other cancers, like breast cancer, patients have lots of treatment choices. We need to maximize the amount of information we can extract from liquid biopsies to make decisions that will yield better patient outcomes. Over the past three years there has been progress in analyzing liquid biopsies, from looking only at circulating tumor cells to understanding other cancer dynamics. There is research in combining multiple tests, e.g., cell-free DNA analysis, circulating tumor cells analysis, and single cell genomics analysis of the circulating tumor cells, enabling better targeting of cancer treatments. And new biomarkers are being researched in liquids which can predict disease progression and target cancer cells, such as a replacement for the PSMA PET test.