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Donation Account: IBAN AT65 6000 0005 1004 5254, BIC BAWAATWW, DEBRA International, Am Heumarkt 27/1, 1030 Vienna

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Skin cancer in EB

Why is cancer research important?

Squamous cell carcinoma (SCC), a type of cancer, is a major cause of death among people with recessive dystrophic epidermolysis bullosa (RDEB). It is widely accepted among senior EB clinicians and researchers that SCC reduces life expectancy in this group of people with EB by an average of 35 years, although some people will be affected at a younger age, and others when older, or in some cases, not at all. Although this type of cancer also occurs in people with normal skin, the SCC in people with RDEB is much more aggressive and very difficult to treat successfully.

For this reason, understanding what causes this cancer, and why it is so much more aggressive and invasive in people with EB, is one of DEBRA International's research priorities. A better understanding could lead to more effective ways of treating SCC, to slow its progression, or even reduce the likelihood of the cancer developing in the first place.

Other types of skin cancer can also occur more frequently in people with other types of EB, but most of these are usually more easily treated. For example, people with EB simplex Dowling-Meara seem to be at a slightly higher risk of developing BCC (basal cell carcinoma), a cancer that also occurs in normal skin, and some people with JEB may be at a higher risk of SCC.

Until recently, little research has taken place to understand the nature of SCCs in EB, i.e. why people with the condition have a so much higher risk of developing these cancers and why fatality is so much more common than in the population at large.

Given the rarity of EB, there is minimal interest so far from commercially or publicly funded research programmes into cancers associated with the condition or in understanding their causes. DEBRA, therefore, has concentrated its funding on projects that lead to a specific increase in the understanding of cancers in EB so that, as the state of knowledge about cancers in general increases, we will be able to more easily identify those elements that have a relevance to EB.

How will understanding the cause of cancer in EB lead to therapies?

Cancer is a result of the normal control processes in cells which make up the body's tissues going wrong: the cancer cells that result behave abnormally in their metabolism and growth characteristics. Cancer cells are no longer subject to the mechanisms that ensure normal cell growth, division and cell death, and this can lead to tumour formation and spread. This altered behaviour is because of changes in the activity of the cancer cell's own genes: some genes may be inactivated, others activated, or active at much higher or lower levels than in normal cells.

Cancer can be difficult to treat because the differences between cancer cells and the body's normal cells may be quite subtle – any drug which kills cancer cells is often quite toxic to the normal cells too.

Identifying the changes in gene activity that occur in cancer cells, and how they might be controlled, could lead the way to effective anti-cancer drugs. Understanding why EB cancers are much more aggressive than cancers in normal skin can also be investigated in the same way and may lead to clues to developing EB-specific drugs.

For this reason, much of the research funded by DEBRA studies how EB SCC cancer cells differ from SCC in normal skin, and from EB skin that has no cancer – with the goal of identifying gene targets for which drugs can be developed.

Why might EB skin be more prone to developing cancer?

There are several possible reasons identified so far. Several of the skin proteins that we know to be faulty in EB, such collagen 7, laminins, or integrins, are important not only for the structural strength of the skin. These proteins also interact with other proteins present in the skin, some of which are important in a wide variety of cellular control mechanisms. If the EB protein is faulty, some of its interactions may also be faulty, disrupting normal cellular processes.

In addition, SCC seems always to develop in areas of chronic wounds in skin. In healing wounds, many genes involved in skin repair are switched on, or active at very high levels – in chronic wounds, these processes can become permanently altered so that they no longer switch off, therefore disrupting the wound healing cell processes. For this reason, avoiding the development of chronic wounds in EB skin is important, and helping chronic wounds to heal appropriately while avoiding triggering cancer development will also benefit from a better understanding of what is happening at the cellular and genetic levels in wounds.

Furthermore, the structural weakness of EB skin may contribute directly to cancers which have already developed being able to spread: cancer cells are more easily dislodged as skin is damaged, and can travel into the blood system around the body.

DEBRA International's research into wound healing and skin cancer is therefore very closely linked. A new area of research since the EB 2009 research conference is studying what happens in areas of skin inflammation associated with chronic wounds – this could lead to anti-cancer treatments, as well as better ways of helping chronic wounds heal.

Some current priorities for research into cancer in EB

  • Identifying the genetic and cellular characteristics of EB skin that make it more prone to SCC development, and metastasis (spread).
  • Identifying the changes in EB SCC that may provide targets for anti-SCC drug development.
  • Collecting and characterising patient SCC tissue biopsies as a research resource.
  • Understanding how chronic wounds and inflammation trigger SCC initiation, and identifying druggable targets.