Tanning Beds Cause 170,000 Skin Cancers In USA Annually

Editor's Choice
Academic Journal
Main Category: Melanoma / Skin Cancer
Also Included In: Dermatology;  Cancer / Oncology
Article Date: 03 Oct 2012 - 10:00 PDT



View the Original article

Researchers Find Cause Of Chemotherapy Resistance In Melanoma

Researchers with UC Irvine's Chao Family Comprehensive Cancer Center have identified a major reason why melanoma is largely resistant to chemotherapy.

UCI dermatologist Dr. Anand Ganesan and colleagues found a genetic pathway in melanoma cells that inhibits the cellular mechanism for detecting DNA damage wrought by chemotherapy, thereby building up tolerance to cancer-killing drugs.

Targeting this pathway, comprising the genes RhoJ and Pak1, heralds a new approach to treating the deadly skin cancer, which claims nearly 10,000 U.S. lives each year. Study results appear online in Cancer Research, a journal of the American Association for Cancer Research.

"If we can find a way to turn off the pathway responsible for this resistance, melanoma tumors would suddenly become sensitive to therapies we've been using for the last 20 years," said Ganesan, assistant professor of dermatology and biological chemistry at UCI.

In pursuit of a cause for the chemo tolerance, he and his colleagues performed a genome-wide scan for genes controlling drug resistance in melanoma cells. Their search identified RhoJ, a gene normally involved in blood vessel growth. They saw that in response to drug-induced DNA damage in a melanoma cell, RhoJ activated another gene, Pak1, which initiated a molecular cascade suppressing the cell's ability to sense this damage - and blocking the apoptosis process.

"Normally, such drug-induced DNA damage would result in cell death," Ganesan said. "But this blunting of DNA damage response allows melanoma cells to mutate and proliferate. Being capable of rapid adaptation and change is a hallmark feature of this challenging form of cancer and makes it very difficult to treat."

On the heels of this discovery, he and colleagues have begun exploring methods to inhibit the genes responsible for this DNA damage tolerance. What they come up with could one day supplement chemotherapy treatments for melanoma, Ganesan added.

View the Original article

Biologists Find The Cause Of Pain In The Treatment Of Fair Skin Cancer

Pain caused by 2 different mechanisms

Apply the ointment, light on, light off - that's how easy it is to cure various forms of non-melanoma skin cancer. However, the majority of patients suffer severe pain during the so-called photodynamic therapy. Why the treatment with ointment and red light can be so painful has now been uncovered by researchers from the RUB. They identified the ion channels involved and signalling molecules secreted by the cancer cells. "The results may provide a starting point for suppressing the pain", says Dr. Ben Novak of the Department of Animal Physiology.

How the photodynamic therapy works

In contrast to normal cells, cancer cells are equipped with different enzymes and have a much higher metabolism. If you apply a molecule called aminolevulinic acid to the skin in the form of a gel, cancer cells take up considerably more of this substance than healthy cells. If aminolevulinic acid accumulates in the cells, the mitochondria - the power plants of the cells - form the molecule protoporphyrin IX. When irradiated with red light, protoporphyrin IX reacts with oxygen. This produces highly reactive oxygen species, free radicals, which destroy the cancer cells. Approximately ten minutes of red light irradiation is sufficient to successfully treat superficial forms of non-melanoma skin cancers such as actinic keratosis. Doctors also remove warts in this way.

Painful therapy

"The catch is: it's terribly painful", says Ben Novak. Forty percent of those treated experience pain during the light irradiation, which they assess on a scale of 0 to 10 (whereby 10 corresponds to an excruciating pain like a heart attack) as 7 to 8. Using injections, like at the dentist, it is possible to numb the nerves involved. "But that also always involves a risk", says the Bochum biologist. The scientists led by the RUB professor Dr. Hermann Lübbert have now solved the mystery as to why the treatment hurts at all.

Pain-sensitive cells in the skin are stimulated

The pain is generated by two mechanisms. In a cell culture experiment, the team showed that not only cancer cells but also pain-sensitive nerve cells in the skin take up aminolevulinic acid - and its derivative methyl aminolevulinic acid - from the ointment. Using calcium imaging, the animal physiologists followed the activity of nerve cells which they had treated with aminolevulinic acid and cells that were not exposed to the substance. Treated nerve cells fired when the researchers exposed them to light. In a living organism, this would mean that the cells would send a pain stimulus to the brain. Without the aminolevulinic acid, the pain-sensitive cells remained inactive under red light. In further experiments, the scientists showed that the activity of the nerve cells is caused by sodium channels and voltage-gated calcium channels in the cell membrane. "A drug that targets these channels would, conceivably, be able to suppress the pain - but that's still in the future", says Ben Novak.

Tumour cells alert nerve cells

Lübbert's team found that pain is generated in the nerve cells themselves, but also in another way. The affected tumour cells secrete a molecule - namely acetylcholine. "This is how they pass the message to other cells: something is wrong, my mitochondria are collapsing right now", Novak illustrates. Acetylcholine acts as a neurotransmitter in the nervous system, where it is harmless. "Previous studies have shown though, that it is very painful when it is injected into the skin". Some of the results have already been published. The researchers are currently preparing the data on the mechanisms of pain generation for publication. This attracted a great deal of interest at the 12th Congress of the European Society for Photodynamic Therapy in Dermatology (Euro-PDT) in Copenhagen in May 2012.

View drug information on Photodynamic Therapy.

View the Original article