Emphasis on personalised treatment during 1st International EUOG state-of-the-art conference on kidney and prostate cancer

28 October 2013

On 26-27 September, the European Uro-Oncology Group (EUOG) held the 1st International State-of-the-Art Conference on Kidney and Prostate Cancer in the InterContinental Amstel Hotel in Amsterdam. The speakers, a multidisciplinary group of international experts, discussed new and future treatment strategies.

The first day of the conference focused mainly on kidney cancer. Prof. Tim Eisen (UK) discussed the potency and specificity of more recently tested tyrosine kinase inhibitors (TKI) with superior potency. The somewhat surprising outcome of the latest randomised phase III trials testing axitinib and tivozanib in the second and first line, respectively, did not result in a substantial overall survival benefit in comparison to sorafenib. Eisen questioned whether potency and specificity of TKIs were actually related to efficacy of this class of drugs. Prof. Alain Ravaud (FR) provided an update on the role of mTOR blockade in metastatic ccRCC.

Prof. Susanne Osanto (NL), president of the EUOG, discussed mechanisms of tumour cell resistance, indicated the importance of tumour cell heterogeneity, and drew attention to other novel targets such as stem cells and miRNAs which can be drivers of tumorigenicity. She then reviewed new treatment options, including immunotherapy through PD-1 blockade.

Prof. Steve Campbell (US) spoke about the importance of the quantity of normal kidney spared after partial nephrectomy as one of the main predictor of post-surgery kidney function – the other being pre-surgery renal function. Dr. Karim Touijer (US) put health economic rationale for robotic nephron-sparing surgery in global context and perspective.

A lively debate between Prof. Hein van Poppel (BE) and Prof. Bernard Escudier (FR) followed, arguing that there are more pros than cons when it comes to oligometastastic RCC and the role of metastatectomy. Escudier pointed out that, unfortunately, prospective data are lacking that could provide more compelling evidence in favour of surgery.

Prof. Rob Coleman (UK), Prof. Tia Higano (US) and Prof. Matthew Smith (US) discussed the latest data on bone-seeking drugs applied in metastatic prostate cancer patients, including radium-223 and the Rank-ligand inhibitor denosumab. Coleman discussed local environmental factors that favour the process of metastasis such as PTH and the similarities between behaviour of bone seeking metastatic breast cancer cells and prostate cancer cells.

Synthetic lethality

The key note speaker of the day was Prof. René Bernards (NL), from the Netherlands Cancer Institute (NKI), who introduced the concept of “synthetic lethality” – a term which comes from classical genetics and describes situations in which a mutation and a drug together cause a cell’s death.

Synthetic lethality is a new way to find cancer drug targets. Mainstream cancer drug discovery aims to block oncogenic signalling or, more rarely, to restore tumour suppressor gene function. Synthetic lethality, on the other hand, seeks not to change the characteristically aggressive features of cancer cells but instead to use them to cause the cells’ death.

Surprisingly, using a single compound was unsuccessful, but combining them resulted in lethality of the cancer cells by blocking tow intracellular pathways at the same time. Many such synthetic lethal interactions exist, just waiting to be discovered and mined as anticancer drug targets.

Bernards discussed a new technology named RNA interference (RNAi) which is suitable to find genes that are synthetically lethal. He has developed the use of large-scale RNAi libraries to screen human cells. In RNA interference, small double-stranded RNAs efficiently and specifically silence gene expression by chopping up messenger RNA.

Until recently it was not practical to conduct large-scale screens using RNAi in human cells because of the expenses and labour involved. But now this can be more or less done it in one experiment. Bernards’ lecture raised great enthusiasm amongst the audience and he was able to bridge basic science and clinic.

Personalised treatment

The second day of the meeting focused on prostate cancer and various emerging and future treatment options were discussed. One of the biggest themes of the day was how to move towards personalised treatment strategies.

“Detailed information on patient base line and disease characteristics may allow clinicians to identify specific populations that will benefit most from different drugs,” said Prof. Joaquim Bellmunt (ES) at the end of this presentation on the recently-concluded TROPIC, COU-AA-301, and AFFIRM trials, stressing why this is the way forward in the treatment of cancer.

Several other presentations dealt with the question of how to get this detailed information. New developments in the use of cell lines and androgen receptors (AR), novel ways to use imaging before and during treatment, and reshaping the setup of clinical trials all offer promising possibilities.

The complete version of this article is featured in the upcoming edition of European Urology Today.