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Skin and Dermatology 2019

Beating melanoma with cutting-edge science

Credit: ICR/ Chris Bakal & Oliver Inge

Pictured above: Metastatic mouse melanoma cells spreading on a collagen matrix and imaged by Total Internal Reflection Fluorescence (TIRF) microscopy. Actin in green, focal adhesions in blue, and tubulin in red.

Professor Chris Bakal

Professor of Cancer Morphodynamics at The Institute of Cancer Research, London

New technology is giving my team an unprecedented understanding of how cancer cells grow and spread. I work on a skin cancer called melanoma – the fifth most common cancer in the UK, with around 16,000 newly diagnosed cases each year.

Scientists at the ICR have long been at the forefront of research to better understand melanoma, and our research is behind the discovery of some of the most important new treatments for the disease.

The difference between a fatal and non-fatal cancer is usually its ability to spread around the body – in a process called metastasis. We’re aiming to understand what makes some cancer cells, including melanomas, leave their original site and make that journey to other tissues and other parts of the body.

We know a melanoma cell’s ability to change its shape is a crucial factor in its ability to spread. Metastatic cells can take on many shapes, squeezing through tissues and finding their way into places they should not naturally be. In my team, we aim to develop treatments that ‘freeze’ the shape of cancer cells.

We use a sophisticated microscopy, such as the ‘lattice light sheet’ microscope to illuminate melanoma cells in ultra-fine detail, and to generate many images at very high speed. We combine this microscopy with sophisticated artificial intelligence methods to allow computers to understand how the shape of cancer cells influences their ability to spread round the body.

We have recently discovered genes that allow melanoma cells to ‘shape-shift’, and used Big Data integration methods to develop a ‘postcode’ system that maps proteins in metastatic melanoma cells.

We’re aiming to understand what makes some cancer cells, including melanomas, leave their original site and make that journey to other tissues and other parts of the body.

Drug discovery successes

ICR scientists have also made breakthroughs that have helped transform treatment of melanoma. One of the ICR’s most high-profile successes of recent years was research to understand how mutations in a gene called BRAF could help cause the disease.

Researchers at the ICR played a major role in characterising the BRAF gene and its role in cancer, increasing our understanding of malignant melanoma.

Our work in the laboratory led to the discovery of two BRAF-inhibiting drugs that are now mainstays of treatment for advanced melanoma, buying extra months or years for many thousands of patients around the world.

One of these drugs was discovered by a team, which included Dr Olivia Rossanese – who is now the Head of Biology in our Division of Cancer Therapeutics, working to find the next generation of cancer drugs.

Our success at the ICR in discovering new drugs is underpinned by gaining a deeper understanding of the biological processes at work in cancer.

What’s really important for us is to understand the underlying mechanisms and genetic alterations in cancer that lead to uncontrolled tumour growth and spread. And when we begin to understand those mechanisms, we really have a good idea of what the targets are for therapeutics.

Immunotherapy treatments for melanoma

ICR researchers are also leaders in the field of immunotherapy. Recent clinical trials involving our researchers have led to the approval of new immunotherapies for patients on the NHS and worldwide to treat advanced melanoma and other cancers. These treatments have included a highly innovative viral immunotherapy made up of a genetically modified form of herpes simplex virus type-1.

Professor Kevin Harrington, Professor of Biological Cancer Therapies at the ICR and Consultant Clinical Oncologist at The Royal Marsden, was the UK leader of the definitive trial that showed the benefits of this drug, which uses a genetically altered virus to burst cancer cells from within and attract the immune system to tumours.

Research at the ICR has led to vital new drugs to treat melanoma, and a better understanding of its biology than ever before. Together with my colleagues, I am determined to keep on building on what is known about this disease, and find more new ways to treat it.

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