Translate the new findings to enhance treatment of patients with malignant melanoma cancer researchers.

From translational researchers at UCLA's Jonsson Comprehensive Cancer Center (number of days), published results of a study provide insightful journal Cancer found BRAF inhibitor resistance two key areas critical to tumor how two back-to-back: focus and use to learn how to be resistant to melanoma tumor cells inhibitor with cell signal transduction pathway BRAF-mutant, evolve and limited development cell BRAF inhibitor drug resistance is how black keys.

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History of Prostate Cancer Tied to Higher Odds for Melanoma

Studies followed thousands of white male health professionals

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Longest follow-up of melanoma patients treated with ipilimumab shows some survive up to ten years

Sep. 27, 2013 — Patients with advanced melanoma, who have been treated with the monoclonal antibody, ipilimumab, can survive for up to ten years, according to the largest analysis of overall survival for these patients, presented at the 2013 European Cancer Congress (ECC2013).

Professor Stephen Hodi (MD), Assistant Professor of Medicine at the Dana-Farber Cancer Institute (Boston, USA), told the congress: "Our findings demonstrate that there is a plateau in overall survival, which begins around the third year and extends through to the tenth year.

"These results are important to healthcare providers and patients with advanced melanoma since they provide a perspective on long-term survival for ipilimumab patients who are alive after three years of treatment. Our data, which represent the longest follow-up of the largest numbers of patients on any globally approved melanoma therapy, will provide a benchmark for future medicines for advanced melanoma."

Ipilimumab is a human monoclonal antibody that activates the immune system to fight melanoma skin cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). In melanoma, CTLA-4 is inhibited from recognising and destroying cancer cells, but ipilimumab turns off the inhibitory mechanism, enabling CTLA-4 to continue killing the cancer cells.

It is already known that some patients treated with the drug survive for long periods, with one phase III clinical trial showing an overall survival rate of 18% after five years. Therefore, Prof Hodi and colleagues from Germany, France and the USA collected data on 1861 patients in 12 prospective and retrospective studies to provide a more precise estimate of ipilimumab's effect on long-term survival. In addition, they analysed data from a further 2985 patients who had been treated with the drug but were not part of any clinical trial, giving the researchers data on a total of 4846 patients.

The analysis of the 1861 patients showed that the median overall survival was 11.4 months (11.4 being the middle number separating the higher half of the patient survival time from the lower half). "Among these patients, 254 patients (22%) were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%. The longest overall survival follow-up in the database is 9.9 years," said Prof Hodi.

"The plateau, which started at three years and continued through to ten years, was observed regardless of dose (3 or 10 mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug. However, as this was not a randomised comparison, one cannot draw direct conclusions on differences between the doses or the populations."

When data from the total 4846 patients were analysed, the median overall survival was 9.5 months, with a plateau in overall survival starting around three years for 21% of the patients. "This slightly lower survival rate was because there were limited and incomplete data on overall survival, and patients given ipilimumab through the extended access programme tended to be more ill and with more advanced disease," explained Prof Hodi.

He concluded: "The limitation of this study is that it is a pooled analysis from phase II, phase III and observational data and not from a single randomised, controlled study. However, these results are consistent with our findings from randomised clinical trials and confirm the durability of the plateau in overall survival, previously shown to extend to at least five years but now shown to extend up to ten years."

Past President of ECCO, Professor Alexander Eggermont, Directeur General of the Institut Gustave Roussy Comprehensive Cancer Center (France), who specialises in the treatment of melanoma, commented: "This pooled analysis clearly demonstrates that ipilimumab can lead to long-lasting tumour control in metastatic melanoma patients. With a response rate of only 10-15%, one can achieve more than 3-10 years survival in 17-25% of patients who have received only a few doses of ipilimumab. Thus, patients apparently can keep residual tumours under control for a long time when the immune system is properly 'reset', and the concept of 'clinical cures' becomes a reality. These survival results could even double or triple with anti-PD1/PDL1 monoclonal antibodies, and metastatic melanoma could become a curable disease for perhaps more than 50% of patients over the coming 5-10 years."

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Longest follow-up of melanoma patients treated with ipilimumab shows some survive up to ten years

Sep. 27, 2013 — Patients with advanced melanoma, who have been treated with the monoclonal antibody, ipilimumab, can survive for up to ten years, according to the largest analysis of overall survival for these patients, presented at the 2013 European Cancer Congress (ECC2013).

Professor Stephen Hodi (MD), Assistant Professor of Medicine at the Dana-Farber Cancer Institute (Boston, USA), told the congress: "Our findings demonstrate that there is a plateau in overall survival, which begins around the third year and extends through to the tenth year.

"These results are important to healthcare providers and patients with advanced melanoma since they provide a perspective on long-term survival for ipilimumab patients who are alive after three years of treatment. Our data, which represent the longest follow-up of the largest numbers of patients on any globally approved melanoma therapy, will provide a benchmark for future medicines for advanced melanoma."

Ipilimumab is a human monoclonal antibody that activates the immune system to fight melanoma skin cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). In melanoma, CTLA-4 is inhibited from recognising and destroying cancer cells, but ipilimumab turns off the inhibitory mechanism, enabling CTLA-4 to continue killing the cancer cells.

It is already known that some patients treated with the drug survive for long periods, with one phase III clinical trial showing an overall survival rate of 18% after five years. Therefore, Prof Hodi and colleagues from Germany, France and the USA collected data on 1861 patients in 12 prospective and retrospective studies to provide a more precise estimate of ipilimumab's effect on long-term survival. In addition, they analysed data from a further 2985 patients who had been treated with the drug but were not part of any clinical trial, giving the researchers data on a total of 4846 patients.

The analysis of the 1861 patients showed that the median overall survival was 11.4 months (11.4 being the middle number separating the higher half of the patient survival time from the lower half). "Among these patients, 254 patients (22%) were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%. The longest overall survival follow-up in the database is 9.9 years," said Prof Hodi.

"The plateau, which started at three years and continued through to ten years, was observed regardless of dose (3 or 10 mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug. However, as this was not a randomised comparison, one cannot draw direct conclusions on differences between the doses or the populations."

When data from the total 4846 patients were analysed, the median overall survival was 9.5 months, with a plateau in overall survival starting around three years for 21% of the patients. "This slightly lower survival rate was because there were limited and incomplete data on overall survival, and patients given ipilimumab through the extended access programme tended to be more ill and with more advanced disease," explained Prof Hodi.

He concluded: "The limitation of this study is that it is a pooled analysis from phase II, phase III and observational data and not from a single randomised, controlled study. However, these results are consistent with our findings from randomised clinical trials and confirm the durability of the plateau in overall survival, previously shown to extend to at least five years but now shown to extend up to ten years."

Past President of ECCO, Professor Alexander Eggermont, Directeur General of the Institut Gustave Roussy Comprehensive Cancer Center (France), who specialises in the treatment of melanoma, commented: "This pooled analysis clearly demonstrates that ipilimumab can lead to long-lasting tumour control in metastatic melanoma patients. With a response rate of only 10-15%, one can achieve more than 3-10 years survival in 17-25% of patients who have received only a few doses of ipilimumab. Thus, patients apparently can keep residual tumours under control for a long time when the immune system is properly 'reset', and the concept of 'clinical cures' becomes a reality. These survival results could even double or triple with anti-PD1/PDL1 monoclonal antibodies, and metastatic melanoma could become a curable disease for perhaps more than 50% of patients over the coming 5-10 years."

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Cutting off all points of escape for melanoma cells

Sep. 19, 2013 — Despite the success of recent approved therapeutics to treat advanced melanoma, metastatic cancer cells inevitably evolve resistance to drugs. In the journal Cell Reports, a team of researchers based at The Wistar Institute, report on the mechanics by which melanoma can evolve resistance to a powerful combination of drugs -- BRAF and MEK inhibitors.

They found that resistant melanomas acquired a mutation in the MEK2 gene and multiple copies of the mutant BRAF oncogene, simultaneously decreasing the sensitivity to both drug targets. Their findings also uncovered a new potential target for melanoma therapy, a protein called S6K. Additionally, early studies in a laboratory model for melanoma show that a triple combination of drug inhibitors halted the growth of resistant tumors.

"Melanoma tumors are particularly adept at rewiring themselves so that anticancer drugs lose their effectiveness, and we must continue to outthink the disease in order to block off all points at which it can evade therapy," said Jessie Villanueva, Ph.D., assistant professor in Wistar's NCI-designated Cancer Center and member of The Wistar Institute Melanoma Research Center. "There are currently therapeutics available that can block the pathway that leads to S6K, but we are also interested in developing inhibitors to S6K itself."

Melanoma is the deadliest, most aggressive form of skin cancer. While surgical treatment of early-stage melanoma leads to 90 percent cure rates, advanced melanoma is notoriously resistant to chemotherapy and has a tendency to metastasize, or spread, throughout the body. According to the World Health Organization, cases of the disease continue to rise internationally, which has helped spur research into therapies such as BRAF and MEK inhibitors.

BRAF inhibitors were developed in response to discoveries that a specific mutation in the BRAF gene was responsible for nearly 50 percent of melanoma cases. The BRAF protein is part of the MAP kinase pathway, a chain of enzymatic reactions -- including the enzyme MEK -- that is commonly over-activated in cancers.

"Combining BRAF and MEK inhibitors was conceived as a one-two punch against the MAP kinase pathway," Villanueva said, "and while it is considered successful in the clinic, some tumors do not respond and others develop resistance, underscoring the need for new therapeutic strategies."

As cancer clinicians began to see patients develop resistance to BRAF and MEK inhibitors, the Wistar team began to explore the mechanisms by which tumors develop resistance. They found that melanoma cells used different tactics for each enzyme. Mutations in MEK2, for example, would render anti-MEK therapies ineffective. To defeat BRAF inhibitors, surviving melanoma cells exhibited numerous copies of the mutant BRAF gene, enough to overpower anti-BRAF drugs.

"There were simply too many copies of BRAF to block, it became a numbers game and the mutation was winning," Villanueva said. "Increasing the dosage of BRAF inhibitors could be one solution, but that cannot be done in patients without causing serious toxic effects."

A possible answer, they reasoned, was in the PI3K/mTOR pathway, a network of signaling enzymes often active within melanoma cells. However, they could find no sign that any of the "usual suspects" -- points along the pathway commonly known to be involved in cancers -- had any evident part in BRAF/MEK resistance. It was not until they examined farther "downstream" that they found persistent activation of S6K, an enzyme that appears to be at the point where P13K/mTOR and MAP kinase pathways merge.

So the researchers tried combinations of inhibitors against BRAF, MEK and PI3K/mTOR (as there are currently no effective S6K inhibitors) in a mouse model of melanoma. "With a triple combination of drugs, the tumors slow down and just stop growing," Villanueva explained.

Although a cocktail of two drugs (a combination of BRAF and PI3K/mTOR inhibitors, for example) might work, they postulated that using three drugs could be more potent and counter intuitively less toxic at the same time. "We followed these mice with melanoma for three weeks, tumors remain stable, and mice did not show any evident signs of toxicity, " Villanueva said

"For patients, it is not a simple matter of introducing triple combination therapies into use," Villanueva said, " but now we have a mechanism and a rational approach to develop both new drugs and more effective combinations aimed at solving drug resistance in melanoma. Our findings might also offer important lessons for other forms of metastatic cancer."

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Identify new targets for treatment of Sanford-Burnham researchers malignant melanoma.

Sanford Burnham Medical Research Institute, scientists announced discovery of an important role in the progression of the play development of genes, enzymes, and inositol phosphorus lipid dependent kinase 1 （ PDK1) and malignant melanoma. It offers new approach to disease treatment available in an advanced online publication gene finding with this life-threatening.

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Potential immune therapy target for the treatment of malignant melanoma of the identification of seven

Use your own digital technology to count the NCI scientists and tumor tissue of small RNA molecules for identifying melanoma treatment of seven potential immune therapy target. Immunotherapy works by that increase the body's immune system or by using immune cells to attack the cancer cells of a particular type. Overexpression of the success of this treatment for melanoma and cancers of all forms, or very active, is contingent upon finding a protein target cancerous tumor cells have limited expression in normal tissues. 7 That is identified in this work meets the requirements of these gene target. The results of this study led by NCI Division of Cancer Research Center for tumor immunology, surgery branch Morgan Dr. Richard a. 9/10/2013, appeared in clinical cancer research.

Designed a genetic probe containing 97 Morgan and his colleagues looking for a target on the new treatment for malignant melanoma, 72, was considered immune therapy for potential candidate genes and gene sets. Genetic probes for each permit individual RNA molecules accurately count NCI research team, a unique fluorescent barcode had. 59 By using probe isolated researcher in melanoma tumor samples and genetic material RNA to protein, the code sets, and counted each time the barcode gene have been observed. The results of this experiment, scientists concluded 33 of 72 potential target genes overexpression of more than 20% of the malignant melanoma tumor samples. 20 And is expressed in normal tissue samples of tumors of those genes, different methods were identified. Based on this analysis, the researchers conclusions 7 gene warrant potential as a target for immunotherapy of further consideration: found high expression in a large percentage of CSAG2, MAGEA3, MAGEC2 and IL13RA2, PRAME, CSPG4, and SOX10, tumor samples that had limited expression in normal tissues.

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Health Tip: Are You at Risk for Melanoma?

(HealthDay News) -- Melanoma is a dangerous form of skin cancer. Knowing your risk factors may help prevent melanoma and detect it early.

The U.S. National Cancer Institute says risk factors for melanoma include:

Significant exposure to sunlight's ultraviolet rays. Sunscreen can help prevent UV rays from damaging the skin.Use of tanning booths.Having had a severe, blistering sunburn.Living in an area where the sun is strongest.Having a personal or family history of skin cancer.Having 50 or more "common moles." Having very fair skin that burns easily.

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Experimental Melanoma Vaccine Shows Promise in Study

THURSDAY, July 11 (HealthDay News) -- Six of seven advanced melanoma patients had a positive response to an experimental vaccine, a finding that shows promise for personalized skin cancer treatment, researchers report.

The vaccine also slowed tumor progression in three of the patients, according to the investigators at the Washington University School of Medicine in St. Louis.

This cutting-edge approach -- considered by many the future of cancer treatment -- uses a patient's own cells to enhance an immune response to the attacking cancer cells and slow their growth, the study authors explained.

"This is personalized immunotherapy," said senior researcher Dr. Gerald Linette, an associate professor of medicine and neurosurgery.

Melanoma is the deadliest of skin cancers. Each year in the United States more than 76,000 cases of melanoma are diagnosed, and nearly 10,000 die from the disease, according to the U.S. National Cancer Institute.

The immune system plays a part in melanoma, Linette said, and the researchers wanted to see if a molecule called interleukin 12p70 could mount an immune response against the cancer.

"The results show that, in fact, interleukin 12p70 was very important in controlling the disease," he said. "It promoted a response where T cells of the immune system act directly against the melanoma."

Some patients make a lot of interleukin 12p70, and those are the patients who did well. But some patients make very little or no interleukin 12p70, and those are the patients who did worse, Linette said. For those patients, another way of enhancing the response will have to be tried, he said.

The study, published online July 11 in the Journal of Clinical Investigation, discusses use of the vaccine on seven patients with recently diagnosed stage IV cancer, meaning the cancer had spread to other areas of the body.

Dr. Michele Green, a dermatologist at Lenox Hill Hospital in New York City, said, "This is a great first step."

Techniques such as this will be standard some day, she believes. "We are at the infancy of this, but this is going to end up being the way we cure cancer," Green added.

Currently, the prognosis is bleak for late-stage melanoma, Green noted. "If you have advanced melanoma, there is no treatment," she said.

The experimental vaccine is made from a patient's dendritic cells, which is a type of immune cell. The researchers modified the cells to increase production of interleukin 12p70, which stimulates a robust immune response to the cancer, Linette explained.

The research team was able to activate these dendritic cells before giving them back to the patient, he said.

The vaccine seems safer than earlier attempts, but it will be years before such an approach might be put into practice. For now, no clinical trials are planned, Linette said.

"Scientists have been testing vaccines in cancer patients for about 15 years, and the results have been rather discouraging," Linette added. "It's going to take at least five to 10 years more testing before scientists agree what's the best dendritic cell vaccine."

More information

For more information on melanoma, visit the U.S. National Cancer Institute.

SOURCES: Gerald Linette, M.D., Ph.D., associate professor, medicine and neurosurgery, Washington University School of Medicine, St. Louis, Mo.; Michele Green, M.D., dermatologist, Lenox Hill Hospital, New York City; July 11, 2013, Journal of Clinical Investigation, online

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Oregon Woman Tans Her Way to a Melanoma Diagnosis

FRIDAY, June 21 (HealthDay News) -- Katie Wilkes was just 23 years old when she noticed a strange spot on her right breast.

"It was darker than many of my other freckles or moles -- not quite black, but it was dark," said Wilkes, who lives in Portland, Ore. "I asked my boyfriend at the time if I should have it removed. He told me it was 'cute' and that I shouldn't worry about it, so I didn't."

At least not at first. But Wilkes eventually decided to have the unusual spot checked out.

"I made an appointment with a dermatologist for a routine skin check," she said. "I had recently quit using tanning beds, and I felt like I could sleep better at night knowing that a doctor had looked me over and everything was OK."

However, everything wasn't OK. She said that her doctor thought the spot looked slightly abnormal but didn't seem too concerned and sent some tissue to the lab for further examination.

"I was pretty shocked when I got the call that it was malignant," Wilkes said.

So-called "malignant melanoma" is the most dangerous form of skin cancer. If it isn't caught early it can quickly spread to other parts of the body. When melanoma spreads, it can be deadly, according to the American Academy of Dermatology.

Wilkes was lucky she'd decided to go in when she did as the cancer was still at a treatable stage. "Fortunately, my melanoma was relatively shallow and it hadn't spread to my lymph nodes," she said. Treatment took just one surgery to remove the melanoma, but it required a 3-inch-wide, eye-shaped incision.

Although it's impossible to know the exact cause of her melanoma, Wilkes and her doctors suspect that her multiyear tanning bed habit while a teenager contributed to the cancer. The cancer developed in an area that is normally covered by a bathing suit or other clothing but is often exposed when using a tanning bed.

"I recently went for a checkup, and one of the residents said, 'Wow, you had a melanoma when you were 23? Did you use tanning beds a lot as a teenager?'" Wilkes said.

"You couldn't pay me to use a tanning bed now," she noted. Nonetheless, it took some time for that belief to settle in. "I was teased a lot as a kid for having very pale skin, so it's taken a while for me to become comfortable with and eventually embrace my natural skin color," Wilkes said.

Now 26, Wilkes blogs about her melanoma experience and about coming to terms with her pale skin. "I used to hate it when people would preach to me about using tanning beds, so I try to tackle the subject in a down-to-earth, non-preachy way," she explained.

Because she's already had melanoma, Wilkes has an increased risk for developing another melanoma. "I love spending time outdoors, and I'm still a little jealous of my friends who may not need to be as cautious about burning, but I know tanning isn't an option for me anymore," she said. "Once you've had melanoma, you're more likely to get it again, so I do everything I can to avoid sunburns."

She also visits her dermatologist regularly and checks her skin once a month to look for any new growths.

"Melanoma is not just the type of skin cancer you can cut off and forget about," Wilkes said. "It can grow from stage I to stage IV in a heartbeat, and it's incredibly hard to treat when it's not caught early."

More information

The U.S. National Cancer Institute has more about melanoma.

SOURCE: Katie Wilkes, Portland, Ore.

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Experimental Drug Shows Benefits Against Melanoma in Early Study

SUNDAY, June 2 (HealthDay News) -- A new drug called lambrolizumab appears to improve outcomes in patients with advanced melanoma, according to the results of a phase 1 trial.

Lambrolizumab is an antibody that works by revealing the cancer to the immune system so it can mount a response and kill the cancer cells with few serious side effects, the researchers said.

"This is early, but it's very encouraging," said lead researcher Dr. Antoni Ribas, a professor of medicine at the University of California, Los Angeles.

"This is a new class of drugs for cancer that are giving benefits in patients with melanoma, in terms of having a high rate of tumor responses that are durable in patients with metastatic melanoma," he said.

Melanoma is the deadliest type of skin cancer and, until recently, there was no effective treatment, Ribas said. In metastatic melanoma, the cancer has spread.

One of the ways some cancer cells fool the immune system is with a protein called PD-L1 on their surface, which renders the cancer invisible. "PD-L1 is a way the cancer tries to conceal itself or hide from the immune system," Ribas said.

Lambrolizumab blocks the protein and "exposes the cancer to the immune system," he said.

Ribas said that lambrolizumab might also be effective against other cancers, and has already been tested in patients with lung cancer.

The new study was a "phase 1b" trial, which seeks to determine if a drug is safe and also looks for signs of effectiveness. More testing and randomized trials are needed before the drug could become available, Ribas said.

The report was published online June 2 in the New England Journal of Medicine to coincide with the Sunday presentation of the findings at the annual meeting of the American Society of Clinical Oncology in Chicago.

For the trial, 135 patients with advanced metastatic melanoma were placed in three groups and treated with different regimens of lambrolizumab.

The researchers found that, overall, the drug improved cancer in 38 percent of the patients regardless of dose. Specifically, 25 percent of the patients who received the lowest dose showed improvement as did 52 percent of those given the highest dose.

In all, 77 percent of the patients showed some response to treatment, they noted.

How long the positive response lasts isn't known. Five patients were taken off the drug because their cancer worsened. So far the longest response has been over one year, Ribas said.

Most side effects with lambrolizumab were mild and easily managed, he added. These included fatigue, fevers, skin rash, loss of skin color and muscle weakness.

According to Ribas, 13 percent of patients had more serious side effects, including inflammation of the lung or kidney, and thyroid problems.

The research was funded by Merck Sharp & Dohme, the maker of lambrolizumab.

In April, lambrolizumab received "breakthrough therapy" designation from the U.S. Food and Drug Administration, which means the agency will expedite reviewing the data to speed up getting the drug approved, Ribas said.

One dermatologist welcomed the news of the study results.

"I had a patient who was treated with this and it is definitely a lifesaver," said Dr. Doris Day, a dermatologist at Lenox Hill Hospital, in New York City. Before being treated with lambrolizumab her patient had moved to California, but kept Day updated.

Current treatment for advanced melanoma is interferon, which has severe side effects, Day said. "You kind of wish you were dead, because you feel awful," she explained. Lambrolizumab, however, has very mild side effects, she added.

"Life extension is one thing, but if you can't extend life without quality then there's really no point. My patient did well and had good quality of life," Day said.

"Having metastatic melanoma may not be as much of a death sentence as it was," Day noted. "There is hope. There are options now that extend life and quality of life."

More information

To find out more about melanoma, visit the U.S. National Cancer Institute.

SOURCES: Antoni Ribas, M.D., Ph.D., professor of medicine, University of California, Los Angeles; Doris Day, M.D., dermatologist, Lenox Hill Hospital, New York City; June 2, 2013, presentation, American Society of Clinical Oncology annual meeting, Chicago; June 2, 2013, New England Journal of Medicine, online

Copyright c 2013 HealthDay. All rights reserved.

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Immune-Based Drug Shows Promise Against Advanced Melanoma

SATURDAY, June 1 (HealthDay News) -- Nearly one-third of patients with advanced melanomas who received nivolumab, a new immune-based drug, experienced reductions in the size of their tumors, a preliminary study reveals.

Since these types of drugs have typically shrunk tumors in only 5 percent to 10 percent of patients in prior studies, the new results are a boost for immunotherapy generally, the researchers noted.

"I think nivolumab is a real breakthrough drug for patients with metastatic melanoma, and probably for other diseases, too," study author Dr. Mario Sznol, a professor of medical oncology at the Yale Cancer Center in New Haven, Conn., said in a news release.

"The high level of activity observed with this drug opens up a number of avenues for future research to understand and challenge the ways tumors evade the immune system. We're very excited that there is potential for even more activity in combination with other drugs," Sznol added.

One expert not connected to the study was also optimistic about the results.

"Nivolumab shows exciting promise for patients suffering from an otherwise fatal disease -- metastatic melanoma," said Dr. Michele Green, a dermatologist at Lenox Hill Hospital in New York City. "The fact that 30 percent of patients showed improvement from this immunotherapy drug is remarkable since these patients had some of the worse disease."

The study was funded by drugmaker Bristol-Myers Squibb and is scheduled for presentation Saturday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Findings presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.

According to the researchers, nivolumab works by honing in on PD-1 cellular receptors located on immune system T-cells. These receptors are known to function as immune system "gatekeepers," and by working to open such gates the patient's immune system is triggered into cancer-fighting action.

The new study involved 107 patients, all of whom had been previously treated with multiple forms of standard therapies that failed to halt their disease.

Following treatment with one of five different doses of nivolumab, the team found that 31 percent of the patients went on to experience a minimum tumor shrinkage of 30 percent across the various doses.

Forty-three percent of the patients are estimated to have survived two years after treatment, the researchers said, and average survival for patients across all treatment doses is now projected to be nearly 17 months.

In an ASCO news release, melanoma expert Dr. Lynn Schuchter called the results "truly remarkable."

The findings "confirm that 'revving' up the immune system is a powerful approach in shrinking melanoma," said Schuchter, who is also a spokeswoman for ASCO. "Melanoma patients are living longer and better with these new treatments."

However, although the study participants were described as being "typical" patients with advanced melanoma, the investigation's findings are tempered by the fact that it was not a randomized clinical trial and did not compare the impact of nivolumab directly against the performance of other drugs.

"[But] while this was not a randomized clinical trial, it had a considerable number of patients and the durability of responses is a sign of very promising clinical activity," Sznol said in the news release.

A randomized phase III trial has begun, aimed at confirming these initial findings.

Another expert agreed that the drug shows the promise of immunotherapies in general.

"The results of this study are truly remarkable and demonstrate that immunotherapy truly can make the difference for many melanoma patients," said Dr. Yvonne Saenger, assistant professor of hematology/oncology and dermatology at the Icahn School of Medicine at Mount Sinai Medical Center, New York City.

Saenger, who was not connected to the new study, noted that "earlier immunotherapies, such as interleukin 2 and even Yervoy, can only help a small minority of patients," but nivolumab seems to do much better.

More information

There's more on melanoma at the U.S. National Cancer Institute.

SOURCES: Michele Green, M.D., dermatologist, Lenox Hill Hospital, New York City; Yvonne Saenger, M.D., assistant professor of hematology/oncology and dermatology, Icahn School of Medicine at Mount Sinai Medical Center, New York City; June 1, 2013, news release, American Society of Clinical Oncology

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Research Gets to Root of Redheads' Higher Melanoma Risk

THURSDAY, Aug. 22 (HealthDay News) -- It's well known that natural redheads are at higher odds for deadly melanoma skin cancer, and new research in mice may help explain why.

Researchers at Harvard Medical School say the genetic mutation responsible for red hair and light skin also appears to promote a well-known cancer-causing pathway.

A person's hair color and skin tone are influenced by a gene receptor called melanocortin-1 (MC1R), and a mutation in MC1R accounts for the 1 percent to 2 percent of people who are born redheads.

In experiments with mice and cell cultures, researchers found that the same MC1R mutation -- called MC1R-RHC -- triggers a specific biochemical signaling pathway when a redhead is exposed to ultraviolet radiation from the sun and other sources.

This pathway, called P13K/Akt, has been tied to breast, ovarian and lung tumors, according to the study, which was published online Aug. 22 in the journal Molecular Cell.

"[The findings] provide a possible molecular mechanism as to why red-haired individuals harboring [these] mutations are much more susceptible to UV-induced skin damage than individuals with darker skin, resulting in a 10- to 100-fold higher frequency of melanoma," study co-senior author Wenyi Wei, an investigator at Beth Israel Deaconess Medical Center and an associate professor of pathology at Harvard, said in a medical center news release.

The researchers also said their findings are a starting point for future studies. For example, people who carry the MC1R mutation might be identified as being at higher skin cancer risk, or drugs that target the P13K/Akt pathway might help treat certain melanomas.

Melanoma is among the rarest of skin cancers, but it also is the most deadly, accounting for 75 percent of skin cancer deaths, the researchers said.

Researchers note that research conducted in animals often does not have the same results in humans.

More information

The U.S. National Cancer Institute has more about melanoma and other skin cancers.

SOURCE: Beth Israel Deaconess Medical Center, news release, Aug. 22, 2013

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Melanoma May Return Years Later in Some

FRIDAY, June 28 (HealthDay News) -- New research shows that melanoma can recur decades after initial treatment in roughly 9 percent of patients.

The findings show that people who have had melanoma require lifelong follow-up, the study authors said.

The investigators looked at over 4,700 melanoma patients and found that recurrence occurred in 408 patients who had been disease-free for 10 or more years. The recurrence rates were nearly 7 percent after 15 years and 11 percent after 25 years, according to the study in the July issue of the Journal of the American College of Surgeons.

But the researchers also found that patients whose melanoma recurred 10 or more years later were less likely to die than those whose melanoma recurred within three years of treatment. Those with late recurrence were about 40 percent less likely to die of melanoma than those with early recurrence, and those with late recurrence also had a better overall survival rate.

Patients whose melanoma did not come back until at least 10 years after treatment were younger on average than those with early recurrence (age 41 versus 51).

Also, patients with a later recurrence tended to have had an original melanoma with less dangerous characteristics, the researchers noted. They also found that men accounted for 66 percent of patients with early recurrence, compared with 57 percent of those with late recurrence.

"For patients with melanoma, survival beyond 10 years without a recurrence has been considered nearly synonymous with a cure," lead investigator Dr. Mark Faries, a professor of surgery at the John Wayne Cancer Institute at Saint John's Health Center in Santa Monica, Calif., said in a journal news release. "However, most studies do not follow-up patients longer than 10 years. Our study found that late melanoma recurrence is not rare and that it occurs more frequently in certain patient groups," he noted.

"It appears the risk of melanoma recurrence is never completely gone," Faries said. "One change that should result from our study is that people need to be followed-up for life with a physician after a diagnosis of melanoma," he pointed out.

"Fortunately, the vast majority of melanoma patients who remain disease-free longer than 10 years will not have a recurrence," Faries added. "However, patients should be aware that persistent or unexplained symptoms anywhere in the body might indicate a recurrence of their melanoma, and they should return to their physician to make sure the symptoms are not related."

Nearly 76,700 new cases of melanoma will be diagnosed in the United States this year, according to the American Cancer Society.

More information

The American Cancer Society has more about melanoma.

SOURCE: Journal of the American College of Surgeons, news release, June 27, 2013

Copyright c 2013 HealthDay. All rights reserved.

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Young Men Less Likely to Survive Melanoma Than Women: Study

WEDNESDAY, June 26 (HealthDay News) -- White male teens and young adults are more likely to die of melanoma skin cancer than their female counterparts, a new study finds.

Researchers looked at data from more than 26,000 white patients, aged 15 to 39, in the United States who were diagnosed with melanoma between 1989 and 2009 and followed for an average of seven and a half years.

During the follow-up, there were nearly 1,600 melanoma-related deaths. Although males made up about 40 percent of the melanoma patients, they accounted for more than 63 percent of the deaths, according to the study, which was published June 26 in the journal JAMA Dermatology.

After adjusting for various factors, the investigators concluded that males were 55 percent more likely to die of melanoma than females.

Continued public health efforts are needed to raise young men's awareness of the dangers of melanoma, said Dr. Christina Gamba, of the Stanford University Medical Center, and colleagues.

"This alarming difference in the outcome highlights the urgent need for both behavioral interventions to promote early detection strategies in young men and further investigation of the biological basis for the sex disparity in melanoma survival," the study authors concluded.

Melanoma is the third most common type of cancer in American teens and young adults.

More information

The American Cancer Society has more about melanoma.

SOURCE: JAMA Dermatology, news release, June 26, 2013

Copyright c 2013 HealthDay. All rights reserved.

View the original article here