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Single Cell Profiling to Identify Mechanisms of Tumor Progression in Metastatic Prostate Cancer

Principal Investigators:
Joshi Alumkal, MD (University of Michigan)
Euisik Yoon, PhD, MSc (University of Michigan)

Co-Investigators: Thomas Westbrook, MD (University of Michigan), Arvind Rao, PhD (University of Michigan), Arul Chinnaiyan, MD, PhD (University of Michigan), Zachery Reichert, MD, PhD (University of Michigan), Todd Morgan, MD (University of Michigan)

Description: 

  • We now appreciate that prostate tumors are often heterogeneous, containing a mixture of cells with different behaviors and responses to treatment. Furthermore, some tumor cells can adapt and change over time to assume a different identity that is more like a nerve or brain cell, rather than a prostate cell. This identity switch is most commonly exemplified as neuroendocrine prostate cancer—a form of prostate cancer that is particularly difficult to treat.
  • It is now well-appreciated that analysis of circulating tumor cells (CTCs) from liquid biopsies—blood samples—is one approach to understand the architecture of tumors present within an individual patient more comprehensively. CTCs can be present at high levels in patients with advanced disease and represent an alternative to invasive biopsies for studying tumor biology.
  • Joshi Alumkal and Euisik Yoon have developed a novel technology for profiling individual CTCs from patients with advanced prostate cancer. In this project, the team will use this technology to study molecular features in CTCs at baseline and throughout the course of treatment in patients with newly diagnosed, hormone-naïve metastatic prostate cancer who are starting treatment with androgen deprivation therapy (ADT) and ARSIs. Doing so may identify specific cell populations present from the get-go that are responsible for poor patient outcomes and how specific cell populations evolve to assume other identities after treatment.
  • The team will also profile tissue biopsies to clarify the tumor architecture prior to treatment and to determine how that architecture changes upon disease progression.
  • If successful, the team will establish new blood- or tissue-based approaches to identify patients at high risk of treatment failure, explain how these tumors evade treatment, and nominate new treatment approaches that can be moved forward to clinical trials to improve outcomes for patients diagnosed with particularly aggressive forms of metastatic prostate cancer.

What this means to patients: Approximately one-third of patients with newly diagnosed metastatic prostate cancer do not achieve deep or durable responses following standard of care treatments such as ADT + ARSIs. These patients have very poor outcomes. Dr. Alumkal and team will deploy blood- and tissue-based biomarker tests using liquid and tumor biopsies to identify patients whose tumors are at high risk for disease progression and switching to an even more aggressive form of the disease called neuroendocrine prostate cancer. These results can be used to determine which patients may be best suited for new clinical trials that seek to investigate treatments designed to prevent treatment resistance to ADT + ARSIs and/or tumor switching to neuroendocrine prostate cancer.