Last week more than 100 BHD researchers, clinicians and patients attended the Sixth BHD Symposium and First International Upstate Kidney Cancer Symposium in Syracuse, New York. The Symposium was expertly organised and run by Professor Gennady Bratslavsky, Dr Mehdi Mollapour and their team at SUNY Upstate Medical University. The packed programme featured presentations from several renowned BHD and renal cancer specialists.
In the opening keynote presentation Dr W. Marston Linehan, Chief of the Urologic Oncology Branch at the NCI, NIH, reviewed the genetic basis of kidney cancer and the importance of understanding the underlying biology for development of treatments. The rest of the first day focused on the ongoing BHD and RCC scientific research.
Dr Laura Schmidt reviewed the mutations and presentation of 226 BHD families that are part of the NCI’s programme, and Dr Jorge Toro provided an update on current and emerging techniques to identify FLCN mutations. Dr Elizabeth Henske and Dr Vera Krymskaya focused on FLCN’s function in the lungs and role in cell adhesion that could be associated with cyst formation. Dr Maria Czyzyk-Krzeska discussed a role for FLCN in autophagy targeting the midbody. Dr Mehdi Mollapour discussed interactions between FLCN, FNIP1/2 and the chaperone protein Hsp-90; and Diana Dunn further discussed Hsp90 and the regulation of its co-chaperones in RCC.
A common focus was the impact of altered metabolism in RCC: Dr Damir Khabibullin discussed the role of FLCN-interacting protein PKP4/p0071 in metabolic regulation; Dr Arnim Pause spoke about the impact of increased glycogen production on tumourigenesis both as an energy source and a mechanism to increase hyperosmotic stress resistance; Dr Yu Jiang linked a role for FLCN as a ciliary protein to regulation of mTOR activity and altered metabolism; and Dr Sunil Sudarshan demonstrated that altered metabolism in RCC could also impact cancer cell epigenomes.
Additional presentations detailing model systems for BHD and RCC came from Dr Angela Pacitto who discussed the yeast FLCN/FNIP1 orthologues Lst7/Lst4 and their structural organisation, and Dr Masaya Baba who described the development of a new Xp11.2 translocation mouse model for RCC.
The day ended with a poster session, sponsored by Faculty of 1000, featuring 14 posters from research groups around the world which were assessed by Dr Sunil Sudarshan. First place was awarded to Adam Price, second place to Dr Damir Khabibullin, and third place to Diana Dunn.
The second day of the symposium focused on the clinical science of BHD and RCC and featured a keynote presentation from Dr Robert Uzzo, from the Fox Chase Cancer Centre, on assessing and managing patients’ risk rather than their cancer.
Initially the presentations focused on BHD: Dr Mitsuko Furuya presented data on the 115 Japanese families seen by BHD-NET; Dr Paul Johannesma and Dr Irma van de Beek discussing pulmonary and renal pathologies in Netherlands patients; and Dr Nishant Gupta presented data supporting the cost-effectiveness of HRCT screening for BHD in patients presenting with a pneumothorax. There were additional presentations from the VHL Alliance’s Ilene Sussman on the CGIP databank and Dr Jo Robays on the Belgian guidelines for BHD.
Subsequently the presentations were focused on more general clinical aspects of RCC with Dr Brian Shuch, Dr Haifeng Yang and Dr Fang Ming Deng discussing the varied presentation and histology of various forms of non-clear cell RCC and the impact classification can have on treatment and outcome. Dr Adam Metwalli spoke about the different surgical approaches needed in patients with multifocal RCC to minimise impact on function and outcome. Then Professor Gennady Bratslavsky stressed that surgeons should also know when not to cut in metastatic patients, and when to offer targeted treatments.
Ongoing clinical trials were discussed by Dr Jason Muhitch, who spoke about the AGS-003 immunotherapy trial (discussed in this blog post) and the potential of high-dose radiation to bolster anti-tumour immune responses, and Dr Namita Chittoria who discussed trials for papillary RCC caused by MET mutations.
Thank you to all those who participated in the Symposium and contributed to its success. The Symposium also included a patient-focused session which will be covered in a later blog post.