When it comes to skin cancer, most treatments focus on what happens after the disease takes hold. But Gian-Paolo Dotto – researcher, clinician and entrepreneur – aims to take a new approach, harnessing epigenetics to target the earliest cellular changes and tackle cancer at its root. Drawing on decades of experience in molecular biology and medicine, Paolo spoke to us about how his work in skin cancer brings together science, medicine, prevention and even cosmetics.

Can you tell us a bit about yourself and how you came to specialise in dermatology and cancer?

I started my medical training in Turin and then moved to New York City for a PhD in molecular biology at Rockefeller University. This led me to focus on skin: I was fascinated by how cells are organised and interact and, as a living ‘sandwich’ of cellular layers, skin offers a beautifully accessible system to explore this subject.

Through subsequent research positions at MIT, Yale, Harvard and now the University of Lausanne, my focus has remained on the skin, particularly on the earliest steps of skin cancer development. While many researchers study metastasis and the advanced stages of cancer, I’ve always been drawn to the initial cellular and molecular changes that trigger diseases – changes that can be directly observed in the skin. After all, as the body’s largest organ and its interface with the external world, skin provides a unique opportunity to study cellular structure, environmental exposure and disease development in real time.

You are the president of the International CancerPrev Institute – what is the inspiration for and aim of this foundation?

 The idea for CancerPrev grew out of the realisation that research on the earliest stages of cancer was largely happening in siloes. When attending conferences on cancer, I became aware that molecular biologists such as myself and clinicians rarely engaged in dialogue. It struck me how important it was to bring these worlds together – to bridge research and prevention efforts before the disease advances to such an extent that its effects become irreversible.

Together with my colleague Cathrin Brisken at EPFL, who studies early events in breast cancer, we founded the institute to foster exactly this kind of collaboration. Our goal was modest but focused: to connect scientists, clinicians and epidemiologists in Switzerland and across Europe, encouraging a culture of cancer prevention grounded in molecular biology.

We began by organising small workshops and meetings, believing that ‘small is beautiful’ – that real progress often starts with intimate exchanges of ideas. As part of this, we also invited patient advocates and cancer survivors to share their experiences in powerful, often emotional discussions, reminding everyone involved why prevention matters.

In time, this enabled the institute to run a Marie Curie-funded European PhD programme, a junior membership programme to connect young researchers and clinicians from around the world and various public awareness campaigns around World Cancer Day. Even as we grow, we remain focused on our primary mission of promoting collaboration and early intervention in cancer.

You’re also involved in the business side of things through your recently founded company, EpiKare Bio. How do you plan to position yourself in the skin cancer market?

The market for skin cancer and related conditions is enormous – measured in the billions – and growing. This is driven primarily by the prevalence of skin lesions in fair-skinned populations, particularly among older adults. By the age of 70, roughly 70% of Caucasian people develop some form of precancerous or cancerous skin lesions. Even though many of these lesions are not lethal, they can be physically and psychologically devastating, creating a major burden on healthcare systems and patients alike.

EpiKare Bio will focus on premalignant lesions, known as actinic keratoses, which are caused by chronic sun exposure and can progress to carcinomas if left untreated. The potential market for preventing and treating these lesions is immense – it could be worth as much as $10 billion by 2030. What’s more, because the lesions typically appear on areas that are exposed to the elements, like the face, arms and legs, patients are often just as – if not more – keen to remedy them cosmetically as they are to treat them medically.

Indeed, this intersection between dermatology, oncology and the cosmetics industry presents a unique opportunity. The line between skin health, aesthetic care and cancer prevention is increasingly blurred, and advances in one area often benefit the others. EpiKare Bio aims to build on this overlap, developing a platform that bridges pharmacological innovation and skin health applications to effectively serve as an incubator for both scientific and commercial collaboration.

Can you tell us more about the science behind EpiKare Bio?

EpiKare Bio is founded on the concept of epigenetics – the environmental and behavioural factors that can modify gene expression without changing the underlying DNA sequence. We view skin cancer development as an epigenetic landscape, where these changes can favour or even trigger the progression from premalignant to malignant lesions. EpiKare’s mission is to target these epigenetic changes to prevent and/or treat skin cancer more effectively.

Over the years, our research has focused on both the upper (epidermal) and lower (dermal) layer of the skin, which undergo significant age-related changes that can contribute to tumour formation. We have identified a key protein that is involved in both tumour cells and this particular skin layer and, via a collaboration with MIT, we have screened tens of thousands of compounds to develop a first-in-class therapeutic approach.

How do you balance your various different roles in medicine, research and entrepreneurship?

Personally, I focus on science – I know where my strengths lie! In many ways, EpiKare Bio has been made possible by the supportive, collaborative ecosystem we find ourselves in at Biopôle, which has connected us to experienced partners who can work on developing the business, while scientists like myself focus on research.

Still, in the end, all my roles are integrated: I’m just tackling the same problem – skin cancer – from different angles in my respective medical, research and entrepreneurial activities.

One of the most exciting challenges for me is bridging the gap between research and the private sector – in other words, developing interventions with translational significance and real-world impact. Bringing products to market certainly involves overcoming significant hurdles, from conducting clinical trials to ensuring compound stability and safety. To do so, once again, it’s crucial to find the right partners in the pharmaceutical and biotech sectors. I remain hopeful that, together, we will build a pathway to safer, longer-term, preventative treatments for skin cancer.

What innovations would you like to see in this field in the future?

 Looking ahead, I wonder if skin cancer treatment will end up combining molecular approaches with physical therapies. One promising example is laser microfraction technology, developed by colleagues at Harvard, which uses finely spaced laser beams to create microscopic columns of controlled damage in the skin. This stimulates regeneration in the surrounding tissue – and so, it has already found applications in the anti-ageing and skin rejuvenation space. Of course, this is not traditionally a cancer therapy, but the idea of combining chemical and physical interventions offers an intriguing avenue for future exploration – potentially enhancing prevention or treatment in ways that go beyond drugs alone.