Study links widely-used drug azathioprine to skin cancers

A drug used to treat inflammatory bowel disease, arthritis and vasculitis as well as to prevent organ rejection in transplant patients has been identified as an important contributor to skin cancer development, in a research study carried out at the University of Dundee, Queen Mary University of London and the Wellcome Sanger Institute.

The research, published in Nature Communications, identified a `strong case for an association' between the drug azathioprine and the mutational signature found in cases of cutaneous squamous cell carcinoma (cSCC), a common form of skin cancer.

It was already known that use of azathioprine leads to increased photosensitivity to UVA light, probably contributing to development of skin cancers. This new study finds that use of azathioprine leaves a molecular fingerprint in skin cancers, further implicating it in cSCC development.

Charlotte Proby, Professor of Dermatology in the School of Medicine at Dundee, said, "We recommend all physicians give appropriate advice on UVA avoidance including year-round sun protection for their patients on azathioprine."

Professor Proby and colleagues said they were not necessarily advocating withdrawal of azathioprine.

"As with all medications the risks must be balanced against the benefits, particularly with the need to treat potentially life-threatening diseases with an effective drug," she said.

"It is important that sun protection, skin surveillance and early diagnosis/lesion removal are part of the routine management of patients on azathioprine."

cSCC is a common skin cancer with more than 40,000 new cases diagnosed annually in the UK, with significant health economic implications.

Sophia Lowes, from Cancer Research UK, said, "It's important to protect your skin from the sun when it's strong, especially if you burn easily or are taking medications which make you more sun-sensitive. The most effective protection is to spend time in the shade and cover up with a hat, long-sleeved top and sunglasses. For the bits you can't cover, use sunscreen with at least 4 stars and SPF 15 or higher for protection against both UVA and UVB rays."

Importantly, this new study also reveals the molecular landscape of cSCC and highlights potential targets that may be developed for future therapeutic approaches to manage cSCC.

Different carcinogens leave a different `mutational signature' in a cancer. By studying these signatures, researchers can start to determine what the causes of a cancer are.

The researchers in the School of Medicine at Dundee, in collaboration with the Wellcome Sanger Institute and Queen Mary University of London, were able to carry out mutational signature analysis of cSCC tumours from 37 patients, many of whom had been on azathioprine. They found a new mutational signature, Signature 32, which correlated with time on azathioprine therapy.

Professor Gareth Inman, part of the research team at Dundee and now located at the Cancer Research UK Beatson Institute and the University of Glasgow, said, "Although patient numbers were small and these findings should be verified in a larger independent cohort, this molecular study provides a strong case for an association between this novel mutational signature and long-term azathioprine use."

Gareth J Inman, Jun Wang, Ai Nagano, Ludmil B Alexandrov, Karin J Purdie, Richard G Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C Spender, Andrew P South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M Proby, Irene M Leigh.
The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature.
Nature Communicationsvolume 9, Article number: 3667 (2018). doi: 10.1038/s41467-018-06027-1.

Most Popular Now

FDA highlights record-breaking number of generic d…

Today, the U.S. Food and Drug Administration is providing a summary of the generic drug approval actions for the month of October 2018 as part of its efforts to improve p...

FDA approves new drug to treat influenza

The U.S. Food and Drug Administration approved Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older...

Novartis announces clinical collaboration with Pfi…

Novartis announced today that it has entered into a clinical development agreement with Pfizer which will include a study combining tropifexor and one or more Pfizer comp...

Alcon to develop SMART Suite digital health platfo…

Alcon, the global leader in eye care and a division of Novartis, today announced plans to develop the SMART Suite by Alcon, an innovative, digital platform that is design...

Twenty years on, measuring the impact of human ste…

In November 1998, the world was introduced to human embryonic stem cells, the blank slate cells that arise at the earliest stages of development and that go on to become ...

Novartis R&D update highlights industry leadin…

Throughout 2018, Novartis took strong action to focus the company and its capital towards the Innovative Medicines Division, resulting in an industry leading pipeline. To...

Boehringer Ingelheim inaugurates new centre for ag…

Boehringer Ingelheim has taken an important step towards greater agility in the company with inauguration of the new building, called "BI CUBE", at the Ingelheim site. Th...

New epigenetic drug strategy to treat cancer

Researchers have discovered that inhibiting CDK9, a DNA transcription regulator, reactivates genes that have been epigenetically silenced by cancer. Reactivation leads to...

Largest census of cancer genes to help understand …

Researchers at the Wellcome Sanger Institute have created the first comprehensive summary of all genes known to be involved in human cancer, the "Cancer Gene Census". Des...

FDA approves asthma indication for Dupixent® (dupi…

The U.S. Food and Drug Administration has approved Dupixent® (dupilumab) as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years and old...

Can chocolate, tea, coffee and zinc help make you …

Ageing and a low life expectancy are caused, at least partly, by oxidative stress. A team of researchers led by Prof. Dr. Ivana Ivanovi-Burmazovi from the Chair of Bioino...

Agreement with Grünenthal for rights to Nexium in …

AstraZeneca has agreed to divest the prescription medicine rights to Nexium (esomeprazole) in Europe, as well as the global rights (excluding the US and Japan) to Vimovo ...