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
- Department of Urology
- Center for Computational Biology
External collaborations
Publications
Our team
- Martijn Lolkema, principal investigator
- Job van Riet
- Lisanne van Dessel
- Anouk de Jong
- Ronald de Wit
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