Location:Room 14a (ICM, Level 1)
Various mechanisms of resistance have been proposed for different anti-androgens. Specific mutations have been discovered in patients treated with hydroxyflutamide, bicalutamide, or more recently, enzalutamide. Importantly, appearance of truncated, constitutively active androgen receptors during therapy with enzalutamide or abiraterone and clinical implications will be discussed in this session.
The presentation aims to present a concise review of the emerging modern imaging techniques with emphasis on 1) improved assessment of response to therapy in bone metastases and 2) depiction of intra-patient heterogeneity as potential tools for a better understanding of the new AR pathways inhibitors resistance mechanisms.
By using next-generation sequencing on circulating tumor DNA obtained from plasma through a minimally invasive blood test, we have demonstrated the capacity to identify genomic aberrations that associate with resistance to abiraterone.
Institutes: 1Institute of Biophysics, Academy of Sciences, Dept. of Cytokinetics, Brno, Czech Republic, 2International Clinical Research Center, St. Anne´s University Hospital Brno, Center of Biomolecular and Cellular Engineering, Brno, Czech Republic, 3Masaryk University, Department of Experimental Biology, Faculty of Science, Brno, Czech Republic
Institutes: 1Institut Universitaire Du Cancer, Dept. of Urology, Toulouse, France, 2Institut De Pharmacologie Et Biologie Structurale Du CNRS, Dept. of Oncology, Toulouse, France, 3Institut Universitaire Du Cancer, Dept. of Pathology, Toulouse, France, 4INSERM, U1048, Toulouse, France
The prostate is surrounded by adipose tissue (PPAT), an active endocrine organ able to secrete chemokines, referred to as adipokines. Compared to benign epithelium, cancer cells overexpress receptors for adipokines suggesting a crosstalk between PPAT and cancer.
We hypothesized that this could be instrumental in the increased aggressiveness reported in obese cancer patients and in extracapsular disease.
The ability of PPAT to attract cancer cells away from the prostate gland is dependent on an original CCR3/CCL7 axis. Up-regulation of CCL7 secretion in obesity facilitates extra-prostatic extension and local dissemination, which is abrogated when the CCR3/CCL7 axis is inhibited. Attention is driven towards CCR3 antagonists, which are being developed in other medical conditions.