Why does LFS definitely deserve its very first Awareness Day?

Why does LFS definitely deserve its very first Awareness Day?

Opinion
16 March 2020

March 20th is the first ever Li-Fraumeni Syndrome Awareness Day. Never heard of it? That might be because Li-Fraumeni Syndrome (LFS) is a rare genetic disease. As a genetic disease it currently has no treatment, but what it does have is an extremely high risk of cancer, particularly in childhood and adolescence.

Why doesn’t everyone get cancer? Framing the question this way, rather than asking why only some people do, focuses our attention on our natural defences against the disease. Prime amongst these defences is the TP53 gene – popularly known as the ‘guardian of the genome’ and the ‘most important gene in cancer’. TP53 is a tumour suppressor that works to stop individual cells from turning cancerous in response to DNA damage. This is the reason why it is so commonly mutated in tumours – and when it isn’t directly mutated you often find that cancer cells have found ways to disable or get around the anticancer defences controlled by TP53.

But what happens if you are born with a mutated TP53 gene? Li-Fraumeni Syndrome (LFS) is the name given to a cancer predisposition in which people have either inherited a mutated TP53 gene from one of their parents, or else the gene has become mutated in the embryo. The syndrome is named after two doctors, Frederick Li and Joseph Fraumeni, who, in the late 1960s noticed a set of families with rare cancers occurring across the generations – sarcomas, early onset breast cancers and so on. The condition was clearly genetic and later it was confirmed that it was associated with mutations in the TP53 gene.

Things have moved on enormously in the world of cancer since the 1960s, but those initial observations of LFS families are still very much with us. People with LFS carry a hugely increased risk of developing one or more cancers in their lifetime – over 90% for women and around 70% for men. Multiple primary cancers are very common, often starting with cancers in childhood and then subsequent cancers as they get older. While people with LFS can develop all kinds of cancers, there are still some ‘core’ cancers which are most common: bone and soft tissue sarcomas, choroid plexus carcinoma, adrenocortical carcinoma, early onset breast cancer, leukaemia and childhood brain tumours.

LFS is a rare disease and is little known – even many doctors may have never heard of it or come into contact with affected families. For this reason raising awareness is a big theme for patient advocates – and this year two patient organisations, Living LFS in the US and the George Pantziarka TP53 Trust in the UK, are marking the first LFS Awareness Day on March 20th. Using social media, and hash tags such as #WearBlueForLFS, the aim is to spread understanding about the condition, promote understanding and hopefully spread the word to more of the medical profession and the general public.

While there is no treatment for LFS there is increasing evidence that early diagnosis of cancer is especially important for survival. There is now an international consensus on the need for regular whole-body MRI imaging and other screening, now formalised in guidelines from the European Reference Network (ERN) on Genetic Tumour Risk Syndromes (GENTURIS). There is also hope in the increasing amount of research focusing on ways to reactivate mutant p53 proteins, particularly using repurposed drugs (for example we recently highlighted work by Min Lu and colleagues looking at the role of arsenic trioxide).

Finally, we should reflect on two important points. The first is that with the increasing use of genetic testing for cancer predisposition, a key part of Europe’s Cancer Plan, many previously undiagnosed people with LFS will be finally diagnosed. Not only will this make a difference to them, it will also mean that this rare disease will certainly become less rare. Secondly, the more we learn about how to reactivate and manipulate TP53 the more it will feed into the treatment of cancers in people without LFS. Learning more about TP53 ultimately benefits everybody with cancer.

Pan Pantziarka

Pan Pantziarka is Programme Director Drug Repurposing of the Anticancer Fund. He is the co-ordinator of the Repurposing Drugs in Oncology project that the ACF has founded in partnership with the US not-for-profit organisation GlobalCures. By training Pan is a data scientist and author but he has switched fields to oncology. He has previously published in the area of cancer pre-disposition syndromes and is also chairman of the George Pantziarka TP53 Trust.