Liquid Biomarkers of Response and Resistance to 177Lu-PSMA
Abstract
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. The majority of prostate cancer deaths are caused by metastatic disease, where the tumor has spread beyond the prostate. Fortunately, new treatments are emerging to treat this lethal form of prostate cancer. 177Lu-PSMA is one promising new treatment designated as breakthrough by the FDA, which targets a radioactive molecule directly to prostate cancer cells. However, while this treatment can be effective, there are some men who benefit, and others who do not. A test which could tell a physician which patients are most likely to respond to therapy would be hugely beneficial for deciding how to treat patients. Unfortunately, creating and implementing such a test requires tumor biopsies, which are not usually obtained in patients with metastatic prostate cancer. That is because tumor biopsies are invasive procedures and can potentially cause complications. The University of Wisconsin Carbone Cancer Center Circulating Biomarker Core, which I co-direct with Dr. Lang, has developed a new technology that can extract cancer cells and DNA from blood samples instead of needing tissue samples. This allows us to collect tumor samples with much less risk to the patient. Once we have these tumor samples, we can then create a test to identify the men with metastatic prostate cancer who would benefit the most from this new treatment. This test will also identify men who will not benefit, which will allow them to be treated with other therapies more likely to work and spare them the side effects of a therapy that would not help them. In addition, even when treatments work in metastatic prostate cancer, nearly all patients will eventually develop resistance and experience treatment failure and cancer progression. The mechanisms of this are not well understood for 177Lu-PSMA, and this has been historically very difficult to study because it requires tissue sampling at two time-points, before and after resistance, which is not feasible with biopsies. However, using our new blood-based approach, we can now easily collect these samples to better understand resistance, and how to overcome it. Once we know what we are looking for, we can also monitor for resistance in real time each time a patient goes and gets blood drawn. We can identify it early and change treatments before the cancer grows back, which keeps patients healthier and better able to tolerate treatment. The promise of personalized medicine is to match the right patient with the right treatment at the right time. Our team at the University of Wisconsin has pioneered approaches where tumors can be comprehensively studied from only blood samples. This allows for the study of tumors in real time, before, during, and after treatment. There is minimal risk to patients, as metastatic prostate cancer patients are typically getting blood draws frequently just as a routine part of their care. The proposed work will address the FY21 PCRP Overarching Challenges by better defining the biology of lethal prostate cancer to reduce death. By the end of the 3-year grant period, we will have demonstrated the benefit to patients and physicians from our comprehensive liquid biopsy. This is a key step required before we can implement and test the effectiveness of this approach in larger-scale trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210830
Entities
People
- Shuang G. Zhao
Organizations
- United States Army
- University of Wisconsin–Madison