Liquid biopsies in metastatic prostate cancer
Project leader: Johan Lindberg
Keywords: Metastatic prostate cancer, liquid biopsy, circulating tumor DNA, sequencing.
There are multiple emerging avenues for treating and prolonging the life of metastatic prostate cancer patients. The common denominator, not only for emerging- but also for existing therapy, is the need for molecular profiling. Restricting treatment to patients with tumors carrying the specific mutations associated with response to treatment would not only reduce cost, but also avoid unnecessary side effects. However, no such screening tests exist today, neither from commercial- or public providers.
This translational research project aims to establish a sequencing-based profile for accurate detection of all somatic variants associated with response to therapy in metastatic prostate cancer. The profile will be applied to circulating tumor DNA instead of metastatic tissue, which not possible to obtain in a routine clinical setting. Circulating tumor DNA, enriched from plasma, consist of DNA debris from apoptotic cancer cells. In addition, access to the somatic profile of the metastasis, before and during treatment, offers the possibility to monitor how the cancer changes due to the evolutionary pressure of therapy. This will generate new knowledge how to optimize treatment and allow for discovery of novel biomarkers predicting response to therapy.
- Mattias Rantalainen research group, MEB, KI.
- Henrik Grönberg research group, MEB, KI.
- Luc Dirix research group, Department of Oncology, University of Antwerp.
- Mark Divers/James Thompson, KI Biobank.
- Lars Engstrand/Valtteri Wirta, Clinical Genomics Facility, SciLife
Lindberg, J. et al. Tracking the origin of metastatic prostate cancer. European Urology. 67, 819–822 (2015).
Lindberg, J. et al. The mitochondrial and autosomal mutation landscapes of prostate cancer. European Urology. 63, 702–708 (2013).
Lindberg, J. et al. Exome sequencing of prostate cancer supports the hypothesis of independent tumour origins. European Urology. 63, 347–353 (2013).
Klevebring, D. et al. Evaluation of exome sequencing to estimate tumor burden in plasma. PLoS ONE. 9, e104417 (2014).
Whitington, T. et al. Gene regulatory mechanisms underpinning prostate cancer susceptibility. Nat Genet. 48, 387–397 (2016).