Professor Martin Röcken talks to Helen Quinn about the current challenges and opportunities in dermatology treatments, particularly when it comes to immunotherapy for skin cancers, the importance of multidisciplinary working to optimise patient care, and his hopes for the future of the field.
Professor Martin Röcken is established as the chairman of a large dermatology department at the University Hospital Tübingen in Germany and head of the Röcken Laboratory at the same University. He has worked in this department for the past 22 years, overseeing some of the most dramatic developments in dermatology and playing a pivotal role in establishing immune-based therapies in inflammatory skin diseases and oncology.
Having recently concluded his tenure as president of the European Academy of Dermatology and Venereology and as clinical chair, Professor Röcken is committed to advancing knowledge, translating research into treatment advances and improving patient care.
‘There’s a large spectrum of very exciting areas in dermatology. My goal was and is to jointly advance both clinics and research,’ he explains.
Driving dermatology and oncology treatments
Nowhere is this translational research more apparent than in the pioneering oncology work undertaken in the field of dermatology by the Röcken laboratory, especially in developing immune-based cancer therapies.
Professor Röcken explains: ‘The development of cancer immune therapies has mainly come from dermatology. Dermatology has a very strong oncology group that started with the first treatment trials. We pushed it, really, from the beginning.’
The idea of immunotherapy – driving the immune system to be stronger against cancers – evolved around 30 years ago, but there were no sustainable results from studies at the time. The breakthrough occurred when researchers realised that working to get a stronger, more sustained immune response would not work against cancer because the cancer was silencing the body’s immune response to protect itself.
The trials that followed around a decade ago, showed that if, instead of boosting immunity, the immune response was silenced, then a sustained autoimmunity could develop against melanoma metastases, which until then was a tumour resistant to almost all therapies.
‘If melanomas respond to therapy, you may have a relatively quick response; you see what’s happening. As there was no therapy for metastatic melanomas, and as melanomas responded to the first immunotherapy trials, melanomas were originally used to establish immune therapies,’ he explains. ‘Both specific drug inhibiting cancer proliferation and immunotherapy were developed in dermatology over the past 15 years.’
Following the successful trials, immunotherapy was approved for use in melanoma in 2017 and shortly after for other cancer types, including lung, kidney and some types of gastrointestinal cancers.
Skin cancer treatment challenges
Despite notable milestones that have transformed patient treatment, Professor Röcken says many unsolved issues remain. He describes how limitations in immunotherapy emerged earlier than expected, prompting his lab to investigate how the therapy can be used more efficiently and how best to treat patients.
Previously, when a patient had metastatic disease, clinicians would undertake surgery first and then give immunotherapy to prevent the relapse. ‘But what dermatologists realised is that it’s better to first do immunotherapy and then surgery later,’ says Professor Röcken.
For this neoadjuvant therapy approach, dermatology again took the lead, and the concept is now being tested in lung and other cancers.
Finding new ways to treat ‘very difficult cancers’ is also high on Professor Röcken’s radar. For patients who undergo transplant surgery and develop lymphomas of the skin, treatment options can often be limited since the cancer cannot be controlled by treatments which target their immune system.
A new generation of dermatology medications
Alongside the innovations in oncology, the field of dermatology has made significant advances in the treatment of inflammatory and autoimmune diseases. This includes monoclonal antibodies and novel small molecules.
A new generation of drugs that can suppress the immune system – especially antibodies that are highly specific to certain pathways or diseases – are now available to patients.
‘When I started 30 years ago, it was much less satisfactory to treat patients than today. Often when we had patients with joint psoriasis, and we couldn’t treat them sufficiently, and they were desperate. Now they come in, and we can really help them,’ states Professor Röcken.
The new drugs mean there are now more opportunities to treat diseases that were once difficult to treat.
‘We [as clinicians] are now more happy than the patients because they don’t realise anymore what the reality would be without the drug. It’s a nice position to be in, I’m happy, and they consider this normal,’ he adds.
However, Professor Röcken cautions that although these new drugs offer advantages over traditional treatment options, concerns remain about their high cost and widespread use for long-term conditions.
‘The main challenge for the future will be to have a balanced view between the classical drugs and the new drugs to see how long to use them and to know more about their [long-term] safety. Then we can go towards a really bright future for the patients,’ he says.
‘Importantly, we also have to value previous medications such as methotrexate. Some of these drugs are highly effective in terms of treatment outcomes, have very few long-term safety concerns and are not costly at all. They can really help many patients worldwide and should be the first choice to think of.”
Antibody treatments
Researchers investigating treatments for inflammatory disease found that symptoms could be reduced through the use of antibodies. These therapies were originally established in dermatology and rheumatology based on the understanding that they ‘could be used to target distinct pathways, such as the tumour necrosis factor pathway, the interferon pathway, the interleukin-23/17 pathway and the immunoglobulin E pathway’, Professor Röcken explains.
‘These pathways could be blocked with antibodies, which allowed for the treatment of a large spectrum of very different skin diseases. Now, antibodies are used not only for joints and psoriasis but also for a series of other diseases affecting internal organs, like bowel diseases or lung diseases.’
Professor Röcken hopes that new treatments will become more manageable for his patients, and novel ideas are currently being developed. For example, the antibodies currently injected into patients to treat conditions such as atopic dermatitis and asthma will eventually be developed into pills, which will be much more convenient.
Trials are ongoing, alongside the development of other solutions, such as medications that can block not only the soluble mediators that cause the disease but also the signalling. This will give patients new drugs that are as efficient as the antibodies.
Gene therapy
One of the ‘hottest’ new treatment advances for dermatology patients, according to Professor Röcken, lie in the exploration of gene therapies. This area is beginning to offer hope for dermatological patients with rare but severe genetic conditions.
Topical gene therapy is being trialled as an effective treatment for a rare disease in which patients lack the molecule that anchors the upper skin to the lower skin.
‘A cream which contains missing genes goes into the wounded skin and starts to educate it to make the correct molecules. It’s very early, but this shows that you can make gene replacement. One can think of topical gene therapy as replacing genes missing in the skin,’ Professor Röcken explains.
‘It’s fantastic – that’s one of the hottest newest advances. It’s not yet where we want to be, but it shows it works.’
Working across disciplines
The transformative developments in dermatology over recent years would not be possible without input from other areas of medicine. Professor Röcken stresses the importance of multidisciplinary working across all strands of dermatology. ‘We have six to eight hundred new melanoma patients each year, so we have weekly interdisciplinary meetings with colleagues from radiology, internal medicine and surgery,’ he says.
In addition, his hospital department is very closely linked to paediatrics, internal medicine and neurology, facilitating better patient outcomes and exchanging information on the latest developments in order to treat more complex patients through a combined approach.
This collaboration will continue to be required as Professor Röcken focuses his future research on immunogenetics, particularly how genetic factors influence responses to immune-based cancer treatments.
‘What I’m doing now is going beyond to see why some cancers fail despite the best treatment. What are the reasons? Is it the cancer? Is it the patient’s response? So, we go into basic questions to understand where the problems are coming from. And it’s quite promising,’ he says.
There is undoubtedly much more to come from the Röcken laboratory.
