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2024 Stewart J. Rahr Foundation – PCF Challenge Award

Temporal Charting of Treatment-Related Lethal Prostate Cancer Lesions Using Liquid Biopsies and Multi-Region Tumor Sequencing: Development, Testing, and Validation of a Computational Framework Within the PCF SELECT, PRIME, and PEACE Consortia

Principal Investigators: Francesca Demichelis, PhD (Università degli Studi di Trento, Italy), Gerhardt Attard, MD, PhD (University College London, UK)

Co-Investigator: Mariam Jamal-Hanjani, MD, PhD (University College London, UK)

Young Investigator: Yari Ciani, PhD (Università degli Studi di Trento, Italy)

Collaborators: Orazio Caffo, MD (Santa Chiara Hospital, Italy), Umberto Basso, MD (Istituto Oncologico Veneto, Italy)

Description:

  • Precision medicine for prostate cancer, in which treatment eligibility is based on genomic or molecular tumor features, has relied on the ability to obtain and test archived primary tumor samples or newly acquired metastatic biopsies. However, these can be difficult or impossible to obtain and such samples often do not capture the heterogeneity of cancer as it progresses and evolves in a patient.
  • Dr. Francesca Demichelis, Dr. Gerhardt Attard, and team are developing a computational framework to obtain tumor genomic information that characterizes disease heterogeneity over time from plasma tumor DNA obtained from blood draws (a.k.a. “liquid biopsies”).
  • In this project, the team will compile and create a data bank of genomic sequencing data from >1000 individual prostate cancer primary and metastatic samples. This data will be used to define the dynamics of tumor evolution over time and identify genomic alterations that contribute to progression and treatment-resistance. 
  • Computational tools for the charting the genomic evolution of metastatic disease will be developed and validated in a unique cohort of 50 patients with over 20 plasma tumor DNA collections each, taken before, during and after at least 2 lines of treatment, and multi-region post-mortem sampling. 
  • The ability of these computational genomics tools to accurately predict treatment responses and long-term clinical outcomes will be validated in an independent patient cohort.
  • If successful, this project will develop and validate methods to use liquid biopsies to accurately assess prostate cancer disease heterogeneity and evolution, identify new therapeutic targets, track and predict treatment responses, and inform patient management. 

What this means to patients: Precision medicine requires the ability to accurately determine tumor genomic alterations that drive response vs. resistance to different therapies, to guide treatment decisions; however, the historical reliance on static and invasive methods to obtain tumor samples has hampered implementation and success of this approach. Dr. Demichelis and team are developing computational tools to chart when genomic alterations in prostate cancer emerge in relation to treatment regimens, and predict treatment response and clinical outcomes. This will accelerate the successful application of precision medicine for patients with prostate cancer, and ultimately benefit patients with other tumor types.