We are very grateful for the support of The V Foundation for awarding our lab the V Scholar Grant to develop liquid biopies approaches for identifying molecular signatures of treatment resistance in advanced prostate cancer.
This project aims to better characterize the genetic landscape of castration-resistant prostate cancer (CRPC) to uncover genomic alterations implicated in therapeutic resistance. We are using leading research approaches to leverage “liquid biopsies” to address the challenges of tissue inaccessibility and to study the complex evolving genomic landscape of CRPC during the course of therapy.
The ultimate goal of the proposed work is to help reduce mortality from advanced prostate cancer by using innovative approaches and exploiting non-invasive biomarkers in ctDNA to predict treatment outcomes. Metastatic castration-resistant prostate cancer (CRPC) is a lethal disease with no cure. Because the majority of metastases spread to the bone, obtaining tissue biopsies are painful. Furthermore, it is not always feasible to repeatedly perform surgical biopsies during the course of treatment to assess the cancer.
The proposed approaches aim to leverage liquid biopsies as a non-invasive and sensitive screen for circulating tumor DNA (ctDNA) in cancer from patient blood. The detection of ctDNA can be used for monitoring changes in disease burden such as during progression while on treatment or disease relapse. We also propose that ctDNA can be used to identify genetic signatures in CRPC, which can pinpoint specific vulnerabilities of the cancer to therapies.
The translational impact for successfully achieving the goals of this proposed research is three-fold: (1) the development of methods will help to accelerate the use ctDNA for clinical applications; (2) the identification of genomic signatures from ctDNA can be incorporated into the design of new biomarker-guided clinical trial for CRPC; (3) the insights into therapeutic response and resistance learned from this study may reveal new directions in diagnostics and treatment of CRPC. The ability to use minimally-invasive liquid biopsies has the potential to complement or replace tissue biopsies, which will transform the standard-of-care and improve the lives of men with prostate cancer.
This research requires the strong collaborative efforts between computational, experimental, and clinical scientists, embodying the paradigm of “computer-to-bench-to-bedside.” Our key collaborators and partners at the Fred Hutch, Seattle Cancer Care Alliance, and University of Washington Medicine will be instrumental to the success of this project.