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2021 Amgen-PCF Young Investigator Award

Integrated Tissue and Circulating Tumour DNA Profiling to Risk Stratify De Novo Metastatic Hormone-Sensitive Prostate Cancer Prior to Systemic Therapy

Edmond Kwan, MBBS, PhD
Vancouver Prostate Centre

Mentors: Alexander Wyatt, DPhil, Gerhardt Attard, MBBS, PhD

Description:

  • Molecular tumor profiling has enabled profound insights into prostate cancer biology and therapy response. However, the genomic landscape of ‘de novo’ metastatic hormone-sensitive prostate cancer (mHSPC) is incompletely understood, in part due to tumor samples being underrepresented in contemporary studies.
  • A better understanding of mHSPC genomics is greatly needed, focusing on biomarkers to predict which established and emerging treatment options would be most beneficial to individual patients.
  • Dr. Edmond Kwan will use robust and proven genomic sequencing approaches to characterize the genomic landscape of de novo mHSPC in two large patient cohorts of plasma circulating tumor DNA (ctDNA) samples and matched prostate biopsy tissue.
  • In this project, Dr. Kwan will explore the relationship between patient clinical characteristics and ctDNA abundance at the time of de novo mHSPC diagnosis.
  • The effect of short-term androgen deprivation therapy on the amount of ctDNA detectable in blood will also be closely examined.
  • Finally, dynamic changes in the genomic composition of mHSPC derived from tumour tissue and pre-/on-treatment blood samples will be determined to uncover specific genomic aberrations that closely relate to features of disease aggression in de novo mHSPC.
  • If successful, this project will provide the first prospective landscape of genomic alterations in de novo mHSPC, propose new risk stratification frameworks, and identify clinical scenarios where ctDNA testing can complement tumor tissue testing to have the greatest impact on patient management.

What this means to patients: The genomic landscape of ‘de novo’ metastatic hormone-sensitive prostate cancer (mHSPC) is incompletely understood. Dr. Kwan will comprehensively profile mHSPC cases at diagnosis and following treatment with systemic therapies. This will enable development of methods for predicting de novo mHSPC outcomes, broaden understanding of molecular mechanisms of therapeutic resistance, and inform the development of clinical guidelines on genomic profiling in de novo mHSPC. Ultimately, these studies will lead to improved precision medicine and clinical trials for patients with advanced prostate cancer.