Assessment of Circulating Tumor DNA to Detect Metastatic Disease in Primary Prostate Cancer

Abstract

For many years, it has been known that individuals with cancer have higher levels of DNA in the blood. In this project, we propose to develop methodologies and demonstrate the feasibility of quantifying how much of the circulating DNA is from the tumor and whether the amount of circulating tumor DNA correlates with worsening prostate cancer. Because most of the DNA extracted from a sample of plasma (the liquid component of blood) is from normal cells, our proposal also describes that we will overcome this technical challenge by focused sequencing of DNA that we expect to be modified if it is from the tumor. This approach is applicable for men who are just diagnosed with prostate cancer (from a prostate biopsy) as well as those who underwent surgery (radical prostatectomy) and are not receiving any therapy. For low-risk men who have been diagnosed with a low-grade prostate cancer on biopsy (and would otherwise delay surgery), the detection of tumor-specific DNA in the blood may indicate the presence of aggressive disease that should be treated immediately. Similarly, if a man undergoes radical prostatectomy, his urologist will usually monitor PSA (prostate specific antigen) levels after surgery, and rising PSA levels (within 1-5 years) is because cancer cells had migrated out of the prostate prior to surgery and are now forming metastases. For this latter group of men, we propose that the detection of tumor-specific DNA in the blood can predict the presence of metastatic cancer cells before PSA levels rise, and these patients would be candidates for immediate radiation therapy. Because timely treatment correlates with survival, our proposal to use circulating tumor DNA as a diagnostic and prognostic tool can improve patient quality of life by minimizing overtreatment and identifying those patients in need of appropriate intervention.

Document Details

Document Type
DoD Grant Award
Publication Date
Mar 29, 2016
Source ID
W81XWH1510136

Entities

People

  • Adam G Sowalsky

Organizations

  • National Cancer Institute
  • United States Army

Tags

Fields of Study

  • Medicine

Readers

  • Molecular and genetic basis of cancer.
  • Oncology
  • Prostate Cancer Biology.