Home Tags Posts tagged with "malignant melanoma"

malignant melanoma


According to a new research, sunscreen alone should not be relied on to prevent malignant melanoma, a deadly form of skin cancer.

The British researchers back public health campaigns calling for sunscreen to be combined with other ways to protect the skin from sun, such as hats and shade.

The new study, an animal research, published in Nature, reveals more about how UV light induces cancer in skin cells.

Sun exposure is a well-known risk factor for melanoma skin cancer.

Researchers say sunscreen should be combined with other ways to protect the skin from sun, such as hats and shade

Researchers say sunscreen should be combined with other ways to protect the skin from sun, such as hats and shade

But, until now, the molecular mechanism by which UV light damages DNA in skin cells has been unclear.

In the new study, scientists at the University of Manchester looked at the effects of UV light on the skin of mice at risk of melanoma.

This allowed them to examine the effects of sunscreen in blocking the disease.

“UV light targets the very genes protecting us from its own damaging effects, showing how dangerous this cancer-causing agent is,” said lead researcher Prof. Richard Marais.

“Very importantly, this study provides proof that sunscreen does not offer complete protection from the damaging effects of UV light.

“This work highlights the importance of combining sunscreen with other strategies to protect our skin, including wearing hats and loose fitting clothing, and seeking shade when the sun is at its strongest.”

The researchers found that UV light caused faults in the p53 gene, which normally helps protect the body from the effects of DNA damage.

The study also showed that sunscreen could reduce the amount of DNA damage caused by UV, delaying the development of melanoma in mice.

But it found sunscreen did not offer complete protection and UV light could still induce melanoma, although at a reduced rate.

Another concern is the fact that any post-sunburn inflammation has the potential to cause cancer cells to migrate. According a study conducted at the University of Bonn in Germany, there is a strong link between UV-related skin inflammation and the spreading of cancer cells in blood vessels. Essentially this means that a bad sunburn can spread cancer from organ to organ, and it does this through the alteration of pigment cells in the dermis. Thankfully, ointments such as mometasone are able to swiftly end inflammation brought on by too much sun.

Melanoma cells manage to stay alive during treatment with BRAF/MEK inhibitors by shifting how they produce energy, researchers have discovered.

Identifying the mechanism behind melanoma resistance to treatment suggests possible strategy for improvement.

A multi-institutional study has revealed that BRAF-positive metastatic malignant melanomas develop resistance to treatment with drugs targeting the BRAF/MEK growth pathway through a major change in metabolism. The findings, which will be published in Cancer Cell and have been released online, suggest a strategy to improve the effectiveness of currently available targeted therapies.

We were surprised to find that melanoma cells treated with the BRAF inhibitor vemurafenib dramatically change the way they produce energy to stay alive,” says David E. Fisher, MD, PhD, chief of Dermatology at Massachusetts General Hospital (MGH) and a co-corresponding author of the Cancer Cell paper.

While current BRAF inhibitor treatment is a major improvement – shrinking tumors in most patients and extending survival for several months – patients eventually relapse. So there is an ongoing need to improve both the magnitude and durability of these responses.

In about half the cases of malignant melanoma – the most deadly form of skin cancer – tumor growth is driven by mutations in the BRAF gene. Research by investigators at the MGH Cancer Center and elsewhere has shown that treatment with drugs that block BRAF activity temporarily halts tumor growth. Combining a BRAF inhibitor with a drug that targets MEK, another protein in the same growth pathway, strengthens and extends the antitumor response. The current study was designed to investigate how BRAF inhibition changes metabolic activity within melanoma cells and to find other possible treatment targets.

Melanoma cells survive by switching to oxidative phosphorylation to supply the energy they need.

The most common way that cells convert glucose into energy is called oxidative phosphorylation and largely relies on the activity of the cellular structures called mitochondria. Many cancer cells use an alternative mechanism that produces the energy compound ATP without involving mitochondria. A series of experiments by the MGH team revealed that the elevated BRAF activity in BRAF-positive melanoma cells suppresses oxidative phosphorylation by reducing expression of a transcription factor called MITF. Suppressing production of MITF reduced levels of a protein called PGC1α that regulates the generation and function of mitochondria. But melanoma cells treated with a BRAF inhibitor showed elevated MITF activity, along with increased expression of oxidative phosphorylation genes and greater numbers of mitochondria. By switching to oxidative phosphorylation to supply the energy they need, the tumor cells increased their ability to survive in spite of BRAF inhibitor treatment.

These findings suggest that combination treatment with mitochondrial inhibitors could improve the efficacy of BRAF inhibitors in malignant melanoma,” says Fisher, the Wigglesworth Professor of Dermatology at Harvard Medical School.

Several small molecules that target mitochondrial metabolism have been identified by investigators here at the MGH and elsewhere, and laboratory investigations of specific combinations of BRAF inhibitors with mitochondrial antagonists are currently underway.

Melanoma is one of the most aggressive cancers. Only one patient in ten survives after 5 years from diagnosis. It is less common than other skin cancers, but it is much more dangerous if it is not found early. It causes the 75% of deaths related to skin cancer. Treatment consists of surgical excision which is completed by radiotherapy, chemotherapy, immunotherapy.