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research-project
Research project  |  Characterizing and Using the Prostate Cancer Genome

CPCT-02

Using Whole Genome Sequencing data from metastatic prostate cancer lesions we seek to understand the drivers of metastatic prostate cancer biology.

What we do

About our project

Motivation and aim of this project

Metastatic prostate cancer is a deadly disease and knowledge on the genomic background of what drives processes like resistance to anti-hormonal therapies is still lacking.

Using Whole Genome Sequencing (WGS) data we try to understand the clinically relevant heterogeneity. The ultimate aim of this project is to develop novel biomarkers that may be used for prospective stratification of patients to tailor treatment choices.

Execution and collaboration of this project

Together with the Hartwig Medical Foundation and the Center for Personalized Cancer Treatment we are executing prospective trials to collect biopsies of metastatic prostate cancer patients and clinical data.

In collaboration with the Center for Computational Biology we actively seek to identify novel mechanisms and markers of treatment response.

Funding of this project

This project has been funded by different sources. The HMF has provided a large amount of the data. We have received research grants from Astellas and JnJ to analyse the data regarding novel anti-hormonal therapies.

To support the ongoing work we seek additional support from non-for profit organizations such as the Dutch Cancer Foundation (KWF).

Possible impact on patient care

This project has the potential to radically alter the treatment paradigm in metastatic prostate cancer. Our primary analysis already revealed many different subgroups with several potential treatment consequences.

We aim to develop this platform into a true patient selection tool that allows both actual stratification and continuous learning systems through ongoing data acquisition.


Our research focus

Added value of WGS data

The genomic data we are collecting spans the entire genome. In many other studies/ projects targeted sequencing is used to limit the costs associated with sequencing following the hypothesis that only “coding” regions in the genome influence cancer behavior. However, using WGS we very efficiently identify patterns of mutational activity and we believe these data are crucial in understanding the processes that underlie the behavior of prostate cancer.

Mutational processes that lead to novel treatment options

Our data on mutational processes show that in about 1/3 patients we are able to identify a mutational process that could be targeted. These include Micro Satellite Instability and Tandem Duplication rich, for which immunotherapy would be the preferred approach; and Homologous DNA Repair deficiency for which PARP inhibitors and platinum based chemotherapy should be effective.

In the other groups we need more basic science knowledge for true targeted therapy approaches.

Funds & Grants

  • Hartwig Medical Foundation
  • Astellas Pharma
  • JnJ pharma

Collaborations

Internal collaborations

External collaborations

Publications

The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact. van Dessel LF, van Riet J, Smits M, Zhu Y, Hamberg P, van der Heijden MS, Bergman AM, van Oort IM, de Wit R, Voest EE, Steeghs N, Yamaguchi TN, Livingstone J, Boutros PC, Martens JWM, Sleijfer S, Cuppen E, Zwart W, van de Werken HJG, Mehra N, Lolkema MP. Nat Commun. 2019 Nov 20;10(1):5251. doi: 10.1038/s41467-019-13084-7.

Our team

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