Cutaneous melanoma is not the most frequent skin cancer, but it is the most aggressive. It causes 80 % of skin cancer deaths. Every year, around 160,000 new cases are diagnosed, and about 57,000 deaths related to this disease are registered the world over.
Melanoma is a malignant proliferation of melanocytes, which are the cells of our skin that are responsible for producing melanin, the pigment that determines skin and hair colour. When a person is exposed to the sun, the melanin synthesis in the melanocytes is activated to prevent the skin from burning and the epidermal cell nuclei from being damaged. This melanin production makes the skin darken, as the melanin absorbs ultraviolet radiation and neutralises the free radicals it generates, thus protecting us from certain cutaneous diseases.
Melanoma is a very aggressive tumour because it can initially appear with very shallow lesions, little more than a millimetre thick, and spread throughout the body until it generates metastases, which are usually the primary cause of death. Melanoma metastases usually affect the liver, lungs, bones and brain. They are of great concern due to their ability to invade other tissues and for their incidence. The incidence of this tumour has been increasing continuously for more than thirty years related, in part, to sunburn, although this is not the only risk factor.
Ultraviolet radiation and sunburn that occurred in childhood and adolescence are risk factors, given that the skin is an organ with a memory. But not all melanomas appear in zones exposed to the sun. Some are of different origin, which is why it is important to study other risk factors.Some are due to the genetic make-up of the individual. For example, people who have fair skin with numerous moles or who are redheads present greater risk due to their reduced quantity of melanin. On the other hand, there are also other, less well-known factors related to situations of stress, diet and even the microbiota. Many elements of the origin of the melanoma are still to be discovered.
Until a little more than fifteen years ago, the average survival rate of a patient with metastatic melanoma just over a year and only 15 % responded to such conventional treatments as surgery, chemotherapy and radiotherapy. However, much progress has been made, thanks to research, and patient survival and quality of life has improved significantly. Two research projects supported by the ”la Caixa” Foundation are working to advance understanding of the causes of the origin and progression of the melanoma, with the aim of improving diagnosis and available treatments.
Some of our cells can enter into a state of “hibernation”, known as senescence, a defence mechanism against the initiation of a tumour. The cells stop dividing and release substances that slow the progression of neighbouring cells and, consequently, tumour development. Senescent cells are the barrier that tumour cells must overcome to progress and be able to spread. Thus, the greater the number of senescent cells, the greater the difficulty encountered by a tumour to progress. The group led by Fátima Gebauer has deciphered a molecular mechanism that boosts cell senescence, which will enable spread of the tumour to be slowed. The team is now working on the design of new therapeutic targets for the more advanced phases of the disease.
The project led by Marisol Soengas has identified the “distinguishing marks of the melanoma”, a series of proteins and genes that differentiate it from the rest of tumours. In addition, her group has developed the only animal model to date that allows the visualisation in vivo of how tumour cells travel to organs where they settle and metastasise. Work with genetically modified mice now enables the study of new mechanisms and treatments that make it possible to obstruct this journey and slow the metastasis of the melanoma.
Fátima Gebauer Hernández, researcher and coordinator of the Genome Biology programme at the Centro de Regulación Genómica (CRG).
Marisol Soengas, researcher and leader of the Melanoma group at the Centro Nacional de Investigaciones Oncológicas (CNIO).
Pilar Pérez, section head of the Health Area of El Mundo.
Projects supported by CaixaResearch: