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2023 Michael & Lori Milken – PCF Young Investigator Award

Non-Invasive Prediction of Tumor Phenotypes, Therapeutic Targets, and Treatment Response in CRPC using ctDNA

Robert Patton, PhD
Fred Hutchinson Cancer Center

Mentors: Peter Nelson, Gavin Ha

Description:

  • Patients with metastatic castration-resistant prostate cancer (mCRPC) exhibit variable outcomes to most therapeutics. Intra-patient tumor phenotype heterogeneity is a likely driver of treatment resistance and the emergence of plastic tumor subtypes, such as neuroendocrine prostate cancer (NEPC), in patients that fail to respond to these therapies.
  • There is an urgent and unmet need for novel diagnostics and biomarkers which can quantify intra-patient tumor heterogeneity, predict treatment outcomes, and predict the emergence of NEPC and other aggressive tumor subtypes. Cell-free tumor DNA (ctDNA) found in patients’ blood has the potential to noninvasively meet these needs, as it allows for frequent testing to monitor therapy efficacy and potential progression.
  • Dr. Robert Patton is investigating the use of ctDNA biomarkers to monitor for additional prostate cancer phenotypes and to predict outcomes and treatment responses.
  • In this project, Dr. Patton and team will determine the ability of ctDNA profiling to quantify the burden of NEPC in patients beginning treatment with androgen receptor signaling inhibitors (ARSI) and use this information to develop predictive tools.
  • A novel genome-scanning tool will be developed to evaluate ctDNA for the emergence of alternate prostate cancer phenotypes.
  • A methodology will be developed to use ctDNA to evaluate the expression of therapeutic targets such as PSMA and predict responses to treatments such as PSMA-targeted radioligand therapy.
  • If successful, this project will result in the development of novel biomarkers and multi-omic approaches to monitor phenotype heterogeneity and clinically relevant molecular subtypes and predict treatment outcomes using ctDNA.

What this means to patients: Prostate cancer is highly heterogenous and also changes during therapy and disease progression. The development of noninvasive biomarkers to predict these changes and treatment responses will improve precision medicine treatment strategies. Dr. Patton and team will develop ctDNA-based biomarkers and prediction models with the ability to actively monitor treatment, influencing accurate clinical decisions in real time and providing a set of non-invasive, liquid biopsy-based tools to better cater treatment plans to a patient’s individual needs.