Knowledge of overexpressed oncogenes and the importance of the transcription factor ETS-related gene (ERG) and cytokines in relation to individualised therapy in prostate cancer, were examined today during the “Personalised medicine in urological oncology” session chaired by Prof. Zoran Culig (AT) and Prof. Jack Schalken (NL).
Dr. Anna Dubrovska (DE) kicked off the Thematic Session. She discussed that through the potential employment of cancer stem cells as a biomarker for tumour radiocurability, a high total number of cancer stem cells can be indicative for high intrinsic radioresistance of prostate tumour. Additionally, cancer-stem cell-related biomarkers such as tumour size can be indicative of the total number of cancer stem cells.
Dubrovska hopes that in the future the use of well-characterised cancer stem cell markers in clinical studies may facilitate tumour diagnostics, patient prognosis, and prediction of response in order to direct the selection of end-treatment. She also expects that radiation will be used in conjunction with markers to specifically target cancer stem cell population.
Dr. Giuseppina Carbone (CH) stated that aberrant expression of the transcription factor ERG produces profound changes in cell phenotype and has a relevant impact on tumour progression. The degree and the intensity of the ERG-induced alterations varies depending on the cell context. She added that ERG methylation is a critical modification in ERG positive prostate tumours, enabling the activation of a pro-tumourigenic and pro-metastatic programme.
Carbone disclosed that the discovery of EZH2-induced ERG methylation opens new opportunities for development of therapeutic strategies for ERG fusion positive prostate cancer. She said that knowledge of the intermolecular dynamics suggests potential approaches for direct ERG targeting. ERG methylation can be triggered by several events and discovering these mechanisms is a significant priority in the near future.
Although there are dozens of cytokines and cytokine receptors, it seems that IL-6-mediated activation of STAT3 is a principal pathway implicated in promoted tumourigenesis, according to Prof. Anders Bjartell (SE). He stated that STAT inhibitors, particularly direct inhibitors of STAT3, may be a promising way to target tumour cells, the tumour microenvironment, and the immune system, in order to obtain an effective anti-tumour therapeutic response. While the preclinical evidence on direct STAT3 inhibition justifies further development of novel small molecule therapeutics, there are currently no direct STAT3 inhibitors under clinical trial for cancer therapy.
Dr. H. Alexander Ebhardt (DE) delivered his associated abstract presentation and concluded that “using systems pharmacology in target proteomics reveals common escape mechanisms from targeted treatment.”
Closing the session, Dr. Hendrik Borgmann (DE) stated that the novel AR inhibitor ODM-201 shows promising efficacy in the second-line therapy scenario of Enzalutamide-resistant prostate cancer both in vitro and in vivo. In addition, the findings paved the way for clinical trials evaluating ODF-201 in patients with Enzalutamide-resistant prostate cancer.