Clinical-Grade Tumor and Longitudinal Cell-Free DNA/RNA Molecular Profiling to Optimize Treatment in Lethal Noncastrate Prostate Cancer
Abstract
Scientific Objective: This proposal aims to develop and apply a safe, noninvasive way to reveal the genetic composition of the underlying tumor in patients with non-lethal prostate cancer by analyzing their blood plasma samples in the context of a novel clinical trial to discover new genetic markers that can improve treatment options for patients with this disease. Background: Research studies have shown that the genetic composition of cancer can improve our ability to administer optimal treatment options to prostate cancer patients. The main hurdle of obtaining this information is the need to perform biopsy sampling of the tumor. The procedure is risky and associated with complications such as infection and pain. Also, the underlying tumor is highly complex, and one biopsy sample does not capture the full genetic picture. This proposal aims to help these patients by developing a safe and noninvasive way to collect the information that a tumor biopsy may provide. Rationale: Cancer cells release their genetic materials into body fluids, such as blood plasma, as fragments of nucleic acids (DNA and RNA), called circulating tumor DNA or RNA. Sometimes referred to as liquid biopsy, this kind of circulating tumor DNA/RNA in the blood can reveal genetic mutations associated with the underlying tumor in multiple cancer types, including prostate cancer. This genomic information may be useful for treatment decisions, for example, finding a gene that predicts responses to a particular treatment would indicate that the patient should be given the treatment, while failing to find any such mutations would tell the oncologist that perhaps the patient may have minimal benefit from receiving such treatment. Knowing the true genetic nature of each man’s prostate cancer allows physicians to provide the most effective therapy to those who need them while sparing those who do not from adverse side effects of unnecessary treatment. Objectives: This proposal aims to develop a blood test for prostate cancer, looking for genetic markers that guide the optimal treatment decision. We plan to apply this test in the context of a recently established clinical trial that aims to help lethal, high-risk localized or metastatic prostate cancer patients by better understanding the genetics in patients who responded very well to treatment and those who did not respond. This will provide guidance for future decisions on whether to give certain patients the same treatment. Applicability of the research: The tremendous potential of analyzing blood plasma for circulating tumor DNA has already sparked extensive interest across the academic and medical community, as well as commercial industry. The main immediate benefit of this noninvasive diagnostic tool will be to minimize the risk and discomfort associated with biopsy sampling. Upon complete development of this test, we will work with the Molecular Diagnostic Team at MSKCC to implement the test in the clinics so that it will be readily available to patients within 1–2 years of proven utility in the research setting. We will also explore the opportunity to work with external institutions and collaborators to disseminate this technology. This will be a safe blood-based test that can also be used for longitudinal monitoring during active surveillance of disease. The outcomes of the proposed research will allow more efficient, personalized, and precise administration of treatment strategies to improve the clinical outcome and overall survivorship of patients with prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910449
Entities
People
- Howard Scher
Organizations
- Sloan-Kettering Institute
- United States Army