We focus on the behavior of metastatic prostate cancer (PC) with the aim to identify new therapeutic targets and treatment predictive tools. We also investigate the direct role of androgen deprivation therapy (ADT) in the highly metastatic phenotype associated with castration resistant PC (CRPC).
PC is initially dependent on circulating androgens, and therefore ADT is the standard treatment for metastatic disease. The effect is often good, but tumors inevitably relapse in a CRPC form, which is often fatal. CRPC often still expresses androgen receptor (AR), and mechanisms for its ability to grow in castrate testosterone levels includes increased AR expression or sensitivity together with an acquired capacity of de novo steroid synthesis or conversion of steroid precursors to support AR with sufficient ligand for transcriptional activation.
PC mainly metastasizes to bone, where it forms predominantly sclerotic lesions. One part of our research focuses on the mechanisms involved the establishment of tumor growth within the bone marrow and those regulating the phenotype of the growing metastases. The aim with this research is to understand the biology of PC metastasis to bone, and to identify possible therapeutic targets.
The last ten years have largely changed the clinical management of patients with metastatic PC. Many new drugs have been introduced, first in the CRPC phase but many are now also introduced in the hormone-sensitive phase of metastatic PC. This has increased patient survival, but also resulted in an urgent need to find tools to identify the patients that benefit most from the different therapies.
We are using liquid biopsies, such as circulating tumor cells, cell-free DNA, thrombocytes, and plasma samples, to design biomarker tools enabling stratification of patients based on gene expression profiles, DNA modifications, or steroidogenic patterns.
We use molecular and cellular techniques to study interactions between tumor cells and bone. In vivo systems include orthotopic and intratibial mouse xenograft models of human prostate cancer, using MRI as a tool to follow growth and phenotypic changes. We isolate circulating tumor cells (CTCs) using the AdnaGen methodology for gene expression profiling.
Our biobank consists of liquid biopsy samples as well as tissue samples from patients with metastatic PC before and during treatment with different drugs.
Current group members
Karin Welén, PhD, Associate Professor, PI
Jan-Erik Damber, MD, PhD, Professor
Andreas Josefsson, MD, PhD, Associate Professor
Daniel Åhs, PhD student
- Gene expression alterations during development of castration-resistant prostate cancer are detected in circulating tumor cells.
Josefsson A, Larsson K Freyhult E , Damber JE, Welén K. Cancers 2019 Dec 21;12(1).
- AR-V7 expression in circulating tumor cells as a potential prognostic marker in metastatic hormone-sensitive prostate cancer.
Josefsson A, Damber JE, Welén K. Acta Oncologica 2019 Nov;58(11):1660-1664.
- Analysis of regulator of G-protein signaling 2 (RGS2) expression and function during prostate cancer progression.
Linder A, Hagberg Thulin M, Damber JE, Welén K. Sci. Reports 2018, 8(1):17259.
- Circulating tumor cells mirror bone metastatic phenotype in prostate cancer.
Josefsson A, Larsson K, Månsson M, Björkman J, Rohlova E, Åhs D, Brisby H, Damber JE, Welén K. Oncotarget 2018, 9(50):29403-29413.
- Castration is a prerequisite for the inhibitory effect of metronomic chemotherapy on the growth of experimental castration-resistant prostate cancer.
Jellvert Å, Åhs D, Olausson J, Franck Lissbrant I, Damber JE, Welén K. Acta Oncol. 2018, 57(7):895-901.
- Circulating tumor cells as a marker for progression-free survival in metastatic castration-naïve prostate cancer.
Josefsson A, Linder A, Flondell Site D, Canesin G, Stiehm A, Anand A, Bjartell A, Damber JE, Welén K. Prostate, 2017 Jun;77(8):849-858.
- Tasquinimod inhibits prostate cancer growth in bone through alterations in the bone microenvironment.
Magnusson LU, Hagberg Thulin M, Plas P, Olsson A, Damber JE, Welén K. Prostate 2016 Mar;76(4):383-93
- Osteoblasts promote castration-resistant prostate cancer by altering intratumoral steroidogenesis.
Hagberg Thulin M, Nilsson ME, Thulin P, Céraline J, Ohlsson C, Damber JE, Welén K. Mol Cell Endocrinol. 2016 Feb 15;422:182-91
- Osteoblasts stimulate the osteogenic and metastatic progression of castration-resistant prostate cancer in a novel model for in vitro and in vivo studies.
Hagberg Thulin M, Jennbacken K, Damber JE, Welén K. Clin Exp Metastasis. 2014 Mar;31(3):269-83
More group Karin Welén publications on PubMed