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Disease and treatment

More effective ways to treat skin cancer being developed

Nonmelanoma skin cancer is the most common type of cancer. Although it is rarely fatal, it can be extremely incapacitating because it often returns repeatedly. Skin cancer is usually removed surgically, since the side-effects of anticancer drugs are more severe than the disease itself or the drugs are ineffective when used locally. Danish researchers have now developed a technique for delivering anticancer drugs locally and effectively. This will be tested on patients in a clinical trial in 2018.

The Danish Cancer Society says that lung cancer, breast cancer and prostate cancer are the most common types of cancer, but nonmelanoma skin cancer is more frequent than all three together. Although this type of cancer is rarely fatal, it is often ignored even though it seriously affects people’s physical and mental health because it strikes time after time. Danish researchers have now published results that give hope to those affected.

“Using a laser technique, we can make microscopic channels in the skin so we can infuse small quantities of chemotherapy where the cancer is. Our new study has tested this and shown that we can eradicate skin cancer cells with existing types of chemotherapy. Because the drugs exist and have already been approved, we can begin testing this on patients with skin cancer in 2018,” explains a main author, postdoctoral fellow Uffe Høgh Olesen, Department of Dermatology and Venereology, Bispebjerg Hospital.

Too much or too little

The Danish researchers and doctors – in collaboration with experts from Harvard University – will use laser-associated drug delivery to target skin cancer effectively. Although the laser beam penetrates the skin, it leaves the subcutaneous layer undamaged, which allows the chemotherapy to be infused exactly where it is required.

“To eliminate the skin cancer, the affected skin is normally scraped away or removed using radiotherapy. This can result in significant scarring on the face, for example, and skin cancer therefore has major physical and mental effects, especially because surgery may be required numerous times.”

The alternative to surgery would be the anticancer drugs used for treating life-threatening forms of cancer. However, basal cell carcinoma is not a fatal disease, and the systemic side-effects are far too severe in relation to the severity of the disease.

“It’s a bit like shooting a sparrow with a cannon or doing nothing at all. There has not been any middle way. Using laser-associated drug delivery, we can treat only the areas affected, thereby avoiding the many side-effects associated with administering chemotherapy in the whole body.”

Like eliminating a wart

Basal cell carcinoma and squamous cell carcinoma are the main two types of nonmelanoma skin cancer. Basal cell carcinoma accounts for about 80% of all diagnoses and is characterized by genetic changes in the Hedgehog signalling pathway. These genes are essential for human development at the fetal stage and in some adult cells, but they are also overactive in several types of cancer cells. The Danish researchers therefore tested drugs that specifically target these genes.

“We think that vismodegib is an especially useful drug. Other chemotherapy drugs typically have cytotoxic effects on cancer cells in general. Vismodegib, however, specifically regulates the Hedgehog signalling pathway genes GLI1 and PTCH1. It is therefore very effective against basal cell carcinoma. However, if it is administered as a pill, it is expensive and has many side-effects. We hope that we can administer it locally by using our method, which will greatly limit the cost and the side-effects.”

So far, the researchers have successfully tested both vismodegib and standard chemotherapy drugs such as 5-fluorouracil (5-FU) and cisplatin on both live pigs and human cells in the laboratory. The pathway from the laboratory to treating patients is normally long but this is not necessarily the case here.

“The process will be much shorter than normal because the drugs have previously been tested in Phase 2 and Phase 3 trials, so we will not need lengthy trials for these phases and therefore we plan to be able to test this on patients in 2018.”

The researchers hope, in addition to creating more effective treatment, to somewhat dedramatize the disease so that patients experience fewer physical and mental effects.

“Being diagnosed with cancer can be traumatic. And it can be really hard when everyone also plays it down because it is not fatal. We hope that the new treatment will make eliminating the disease as easy as eliminating a wart. This may also help to dedramatize the disease so it becomes less traumatic.”

Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines” has been published in Anti-Cancer Drugs. In 2013, the Novo Nordisk Foundation gave a grant to a main author, Merete Hædersdal, for the project New Targeted Treatment of Skin Cancer using Topical Administration of Anti-cancer Drugs in Combination with Laser-assisted Drug Delivery.