Monitoring Disease Burden and Biology Using Tumor Cell-Free DNA in Metastatic Kidney Cancer
Abstract
Cancers of the kidney and renal pelvis are among the 10 common cancers in the United States. While metastatic kidney cancer is nearly universally fatal, new therapies designed to stimulate the immune system to attack kidney cancer have revolutionized the care of these patients. However, significant challenges persist in caring for them. For example, the only validated method for measuring whether a patient s tumor is responding to immune therapy is to measure the tumor size, typically with computerized tomography (CT) scans every 2 to 3 months. However, interpreting CT scans is problematic. Sometimes tumors appear to grow even if the immune therapy is working. In addition, some metastatic tumors grow in locations difficult to measure via CT scan (e.g., tumors in bone). Finally, if tumors are resistant to immune therapy, there may be a significant lag time between development of resistance and documented tumor growth on CT scans. This "lag" is a lost opportunity to intensify and/or change therapies. Therefore, there is a great clinical need for more accurate and "real-time" assessments of tumor response to immune therapies. Indeed, the Kidney Cancer Research Program (KCRP) has identified surveillance and biomarker development as areas of emphasis in 2019. In addition to these current clinical needs, there are emerging needs for kidney cancer patients on immune therapies. For example, if a patient is on immune therapies and has a "complete response," defined as disappearance of all metastatic tumors on CT scans, there is hope that the patient can eventually stop immune therapy. Stoppage of immune therapy could theoretically save the patient time, money, and inconvenience, and potentially decrease the risk of side effects. However, patients and clinicians are often nervous about stopping immune therapy due to the risk of kidney cancer relapse. A highly sensitive biomarker that could detect the presence of small amounts of cancer (too small to see on CT scans but still associated with increased risk of cancer relapse) could inform patients and doctors regarding when it is safe to stop immune therapies, and when the cancer is relapsing so that therapy can be restarted. Similarly, many patients with no metastatic tumors on CT scans experience cancer relapse after their kidney tumor is surgically removed. While "adjuvant" immune therapies given after surgery are being tested in clinical trials to reduce this risk of relapse, we currently have few molecular tools to identify patients at highest risk of relapse. Sensitive assays that detect the presence of small amounts of cancer (too small to see on CT scans) could help doctors know which patients have the highest risk of relapse and thus have the greatest potential benefit from adjuvant immune therapies. One exciting approach to addressing these pressing clinical needs is liquid biopsies. Liquid biopsies in cancer patients typically focus on analysis of the patient s peripheral blood to detect active cancer. This approach has many benefits including more frequent assessments of the patient s tumors (rather than waiting every 2 to 3 months for CT scans). In addition, liquid biopsies can provide information about the biology of the patient s tumors. Thus, in some cases liquid biopsies may be able to substitute for biopsy of metastatic tumors. This provides a relatively noninvasive and safer option for the patient. Given the promise of these approaches, liquid biopsies have also been identified as a 2019 area of emphasis for the KCRP. In the current proposal, we seek to use liquid biopsies in patients receiving immune therapies for metastatic kidney cancer to measure response to treatment. In addition, we seek to explore how the tumor biology of immune therapy responders and non-responders differ. To accomplish these goals, we seek to use two liquid biopsy techniques. Both techniques analyze DNA released by tumor cells into the peripheral blood, which
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010910
Entities
People
- Scott Haake
Organizations
- United States Army
- Vanderbilt University