November, 2018, the Frezza laboratory at the MRC Cancer Unit hosted a special person: Graham Lovitt, the Co-Chair of VHL UK/Ireland – a patient support group that supports cancer patients affected by VHL (von Hippel Lindau disease), HLRCC (Hereditary Leiomyomatosis and Renal Cell Cancer) , FD (Fumarase Deficiency) and BHD (Birt-Hogg-Dubé Syndrome). Given the Frezza laboratories long-standing interest in HLRCC, it was a privilege for Christian Frezza and his team to host Graham, to find out about his experience with cancer patients, and more importantly, to get to know him as a person directly affected by HLRCC.
The story goes back awhile. Christian Frezza first met Graham Lovitt at the NCRI meeting in 2011, when Christian was a post doc at the Beatson Institute in Glasgow. This was the first session on cancer metabolism ever presented at the NCRI meeting and Graham attended this session to know more about the topic, especially because there was a talk on FH and cancer metabolism. The fact that Graham attended this conference perhaps already spoke for his unique approach to his disease. Graham eventually went on to start his own website on HLRCC and Christian joined it as a scientific member in 2017. Over the course of the year Graham and Christian had several digital exchanges till they finally decided to meet in the flesh in 2018.
That late autumn afternoon, when the quiet Graham Lovitt finally visited Christian and his lab at the Hutchison MRC Research Centre, his interest and enthusiasm for the science had not waned a bit. He discussed the complexity of the disease, discovered tools to investigate how the loss of Fumarate Hydratase causes cancer, slowly but attentively trawled through the Mass Spectrometry room and peered down microscopes to see for himself how tissues devoid of FH looked. He interacted with post-docs in the lab during which he underlined the difficulties for patients with HLRCC in attaining a correct diagnosis before the development of aggressive renal cancer. He also highlighted how his support group could help patients with suspect clinical signs to overcome their fears and ask for genetic counselling. He was acutely aware of the current limitations in the development of pharmacological therapies for rare diseases and how much could and should perhaps be done to make research more translational.
In fact, the story about his diagnosis is emblematic and indicates the difficulty of diagnosis of rare cancers. Graham had retired in February 2009 from being a software quality assurance manager in software configuration management control. In January 2010 he was diagnosed with a Collecting Duct Carcinoma and possible metastasis to lungs as nodules. At this time, he also noticed a small surface skin lesion on the forehead and was seeing a dermatologist for its removal. About 30 years ago he had had an excision of what was diagnosed as a very rare benign ‘piloleiomyoma’ – a tumour of the muscle involving hair. He pondered as to whether it might be useful to tell the dermatologist about this benign condition from many years ago. Having forgotten how exactly to spell piloleiomyoma he “Googled” it. To his great shock the search revealed a connection between it and a rare sub-types of kidney cancer. He spent a day researching and found that skin lesion and renal cancer are part of a cancer syndrome – hereditary leiomyomatosis and renal cell carcinoma – HLRCC! He paused and reflected for long and in the end decided that there was a real possibility that there had been a misdiagnosis of his disease. Luckily, he was taken seriously and referred to an NHS geneticist…Graham was right!
The difficulty behind the diagnosis of a rare cancer syndrome inspired him to become a patient advocate and since then he has been the Vice Chair of the HLRCC Family Alliance, a project of the VHL Alliance. He has published an HLRCC Handbook and created a website for patients. He also started Support groups on Facebook and Smart Patients, which currently reach out to over 450 and 200 people worldwide. He is also the Chair of the VHL UK/Ireland Chair – a registered charity which was established to replace a previous VHL Support charity that had closed down. Till date, under Graham Lovitt, the new charity has raised about £100,000 for research and patient support.
Besides being a patient advocate, he is also actively involved with research. His removed kidney was used in research by the late Dr Patrick (Paddy) Pollard to confirm the presence of a novel post-translational modification triggered by fumarate, accumulated in tumours of HLRCC patients. His kidney (and his name in the authors’ list) features in the paper https://www.ncbi.nlm.nih.gov/pubmed/21630274 “Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.”
Back in the lab, the meeting with Graham was an inspiring and humbling experience for all in the Frezza laboratory. Here was a man who was a living testament to why research should not become an esoteric art confined within the laboratory environment or indeed a publicity gimmick, but must be translated into new therapeutic opportunities for patients, especially in the context of rare diseases where options are so limited or completely missing. It was a reminder as to how each unique patient story represents an additional impetus to making a difference not only in the field of research but in reality to someone’s life.
PS: Graham eventually found that 30-year-old piece of paper with the word “piloleiomyoma” …to think had he seen it before, he would never have Googled its spelling and stumbled upon HLRCC and the journey that it led to!