Researchers' cure of metastatic skin cancer revealed

 

Identifying a patient’s genetic mutation led University of Arkansas for Medical Sciences (UAMS) physician-researcher Ling Gao, M.D., Ph.D., to an existing drug that eliminated the patient’s stage IV Merkel-cell carcinoma. Gao’s findings, made in collaboration with two other UAMS researchers, were published today inThe New England Journal of Medicine. Metastatic Merkel-cell carcinoma is often fatal and there is no effective treatment. Gao’s 86-year-old female patient was diagnosed in 2013 with stage IIIB Merkel-cell carcinoma of the right temple. She had surgery and received radiation therapy in May 2013 and additional surgery in July 2014. In November 2014, doctors confirmed that the cancer had metastasized. Gao, a dermatologist who treats Merkel-cell carcinoma patients from Arkansas and surrounding states, performed genetics tests on the tumor that revealed multiple mutations, including PI3Kδ. Gao was aware that the drug idelalisib is a novel PI3K pathway inhibitor approved by the Food and Drug Administration (FDA) for treatment of B-cell lymphoma, a cancer of the blood. She was also aware of recent studies showing that disruption of the PI3Kδ mutation allows the body to mount an effective antitumor immune response. On the basis of her laboratory work and knowledge of idelalisb, Gao began treatment of the patient with the drug on Feb. 6, 2015. Her findings were published in the Journal in a letter to the editor. Three months after administering the idelalisib, there was no sign of the tumor in the patient’s liver, Gao said Based on what she’s learned, Gao said the case can be made for further study of PI3Kδ inhibitors like idelalisib in solid tumors, not just blood cancers. “The efficacy of idelalisib in our patient provides initial clinical evidence that the targeting of PI3Kδ in Merkel-cell carcinoma is warranted,” Gao said in the letter, which was also signed by UAMS’ Fade Mahmoud, M.D., and Mallory B. Shiver, M.D. Gao also credits support she received from Peter Emanuel, M.D., director of the UAMS Winthrop P. Rockefeller Cancer Institute, and James Suen, M.D., chair of the Department of Otolaryngology-Head and Neck Surgery in the UAMS College of Medicine. Story Source: The above post is reprinted from materials provided by University of Arkansas for Medical Sciences. Note: Materials may be edited for content and length. Journal Reference: Mallory B. Shiver, Fade Mahmoud, Ling Gao. Response to Idelalisib in a Patient with Stage IV Merkel-Cell Carcinoma. New England Journal of Medicine, 2015; 373 (16): 1580 DOI: 10.1056/NEJMc1507446 http://www.sciencedaily.com/releases/2015/10/151016094221.htm

Supplement Linked to Reduction in Skin Cancer Risk

 

Preliminary Australian study saw association between nicotinamide and lower rates By Dennis Thompson HealthDay Reporter WEDNESDAY, May 13, 2015 (HealthDay News) -- A cheap and easily available vitamin supplement appears to reduce a person's risk of skin cancer, new research contends. A form of vitamin B3 called nicotinamide is linked to a reduction of non-melanoma skin cancers by 23 percent when taken twice daily, according to Australian researchers. "It's safe, it's almost obscenely inexpensive, and it's already widely commercially available," said senior author Dr. Diona Damian, a professor of dermatology at the University of Sydney. Nicotinamide costs less than $10 for a month's supply and is available at pharmacies and health food stores, she said. However, more study is needed before researchers can say whether everyone would benefit from the supplement. "It's not something we'd recommend at this stage for the general population," Damian said. The study is slated for presentation May 30 at the upcoming annual meeting of the American Society of Clinical Oncology. Findings presented at meetings are generally considered preliminary until they've been published in a peer-reviewed journal. Funding for this study was provided by the National Health and Medical Research Council of Australia. Skin cancer is the most common form of cancer in the United States, with about 5 million cases treated every year at a cost of about $4.8 billion, Damian said. Common skin cancers tend to grow slowly and can be cured if found and treated early, according to the American Cancer Society (ACS). These types of skin cancer include basal and squamous cell carcinoma. A more dangerous type of skin cancer called melanoma accounts for just 73,000 cases a year, according to the ACS. Ultraviolet rays from the sun cause most skin cancers by damaging the DNA of skin cells, Damian said. UV radiation also hampers the body's ability to fight off cancer, depleting the energy that skin cells need to repair damaged DNA and profoundly suppressing the skin's immune system, she said. Earlier studies indicated that nicotinamide can provide skin cells with an energy boost, enhancing DNA repair and strengthening the skin's immune system, Damian said.

New targeted drugs could treat drug-resistant skin cancer

 

Clinical trials to test the new drugs in patients should begin as early as 2015. Existing drugs target faulty versions of a protein called BRAF which drives about half of all melanomas, but while initially very effective, the cancers almost always become resistant to treatment within a year. The new drugs -- called panRAF inhibitors -- could be effective in patients with melanoma who have developed resistance to BRAF inhibitors. The new study was funded by the Wellcome Trust and Cancer Research UK, and jointly led by scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute. It is published in the journal Cancer Cell. The researchers showed that the new drugs -- provisionally named CCT196969 and CCT241161 -- stopped the growth of BRAF-driven melanomas, including those that had stopped responding to currently available BRAF-targeted drugs. In addition, the new drugs halted tumour growth in cancers in which BRAF-targeted drugs had never worked in the first place -- which happens in around 20% of cases. The researchers showed that these new drugs work because they target both BRAF and the growth pathways that the cells come to rely on when they become resistant. The studies established that for both drugs, a dose of 20mg per kg per day -- which when translated to humans would be achievable by taking in pill form -- caused tumours to regress without significant side-effects. The complex research involved designing and synthesising molecules shaped to overcome major drug resistance cell signalling pathways in melanoma, testing the molecules in cultures of melanoma cells and in mice, and studying of the compounds using drug-resistant tumours from patients grown in mice. Study co-leader Professor Caroline Springer, Professor of Biological Chemistry at The Institute of Cancer Research, London, said: "Melanomas often respond initially to the current generation of treatments, but they inevitably acquire resistance to them, and there is a desperate need for more effective options. "Our new inhibitors are the first in a new family of drugs that attack cancers without allowing them the get-out clause of drug resistance, by blocking multiple cancer proteins at once. We are very hopeful that clinical trials from this series of new inhibitors will begin very soon -- and that they will ultimately become new first or second-line options for patients who, at the moment, exhaust all the available treatments and end up with fatal disease." Study co-leader Professor Richard Marais, Director of the Cancer Research UK Manchester Institute, based at The University of Manchester, said: "Our laboratory study showed that these new drugs deliver multiple blows to cancer by hitting several cell survival routes at once. It's a step on from the drugs that are currently available which can't multitask in this way. "The next step is testing this family of drugs in clinical trials to establish that they are both safe and effective in cancer patients, potentially providing urgently-needed new treatments for patients who have run out of options. The trial is set to open soon and we await the results with great interest." Dr Richard Seabrook, Head of Business Development at the Wellcome Trust, said: "Malignant melanoma is the fifth most common cancer in the UK, with over 13,000 people diagnosed in 2011. Doctors already have front-line drugs to treat melanoma, but many patients gradually develop resistance to them and are left with few other treatment options. This research, which discovered how two newly developed compounds could treat drug-resistant skin cancer, may give hope to the thousands who find themselves in this situation." Story Source: The above story is based on materials provided by Wellcome Trust. Note: Materials may be edited for content and length. Journal Reference: Maria Romina Girotti, Filipa Lopes, Natasha Preece, Dan Niculescu-Duvaz, Alfonso Zambon, Lawrence Davies, Steven Whittaker, Grazia Saturno, Amaya Viros, Malin Pedersen, Bart M.J.M. Suijkerbuijk, Delphine Menard, Robert McLeary, Louise Johnson, Laura Fish, Sarah Ejiama, Berta Sanchez-Laorden, Juliane Hohloch, Neil Carragher, Kenneth Macleod, Garry Ashton, Anna A. Marusiak, Alberto Fusi, John Brognard, Margaret Frame, Paul Lorigan, Richard Marais, Caroline Springer. Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma. Cancer Cell, 2014; DOI: 10.1016/j.ccell.2014.11.006

The skin cancer selfie: Gigapixel camera helps diagnose early

 

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Melanoma is the fifth most common cancer type in the United States, and it's also the deadliest form of skin cancer, causing more than 75 percent of skin-cancer deaths. If caught early enough though, it is almost always curable. Now a camera, capable of taking snapshots of the entire human body and rendering high-resolution images of a patient's skin may help doctors spot cancer early and save lives.

Developed by a team of researchers at Duke University in North Carolina, USA, the "gigapixel whole-body photographic camera" is essentially three dozen cameras in one, allowing the researchers to image the entire body down to a freckle. The research will be presented at The Optical Society's (OSA) 98th Annual Meeting, Frontiers in Optics, being held Oct. 19-23 in Tucson, Arizona, USA.

"The camera is designed to find lesions potentially indicating skin cancers on patients at an earlier stage than current skin examination techniques," said Daniel Marks, one of the co-authors on the paper. "Normally a dermatologist examines either a small region of the skin at high resolution or a large region at low resolution, but a gigapixel image doesn't require a compromise between the two."

Although whole-body photography has already been used to identify melanomas and exclude non-dangerous "stable" lesions, the approach is typically limited by the resolution of the cameras used. A commercial camera with a wide-angle lens can easily capture an image of a person's entire body, but it lacks the resolution needed for a dermatologist to zoom in on one tiny spot. So dermatologists typically examine suspicious lesions with digital dermatoscopy, a technique to evaluate the colors and microstructures of suspicious skins not visible to the naked eyes. The need for two types of images drives up costs and limits possibilities for telemedicine.

The gigapixel camera developed by the Duke University team solves this problem by essentially combining 34 microcameras into one. With a structure similar to a telescope and its eyepieces, the camera combines a precise but simple objective lens that produces an imperfect image with known irregularities. The 34 microcameras are arranged in a "dome" to correct these aberrations and form a continuous image of the scene. The exposure time and focus for each microcamera can be adjusted independently, and a computer can do a preliminary examination of the images to determine if any areas require future attention by the specialists.

Marks pointed out that although the resolution of the gigapixel camera is not as high as the best dermatoscope, it is significantly better than normal photography, allows for a larger imaging area than a dermatoscope and could be used for telemedicine, which could make the routine screening available to a larger number of people, even in remote locations.

The gigapixel imaging technology is based on the multiscale camera design, which is part of the Defense Advanced Research Projects Agency program "Advanced Wide Field-of-View Architectures for Image Reconstruction and Exploitation."

Though the camera will still have to prove effective in clinical trials before becoming routinely available to patients, the researchers have gathered enough preliminary data on a healthy volunteer to demonstrate that it has adequate resolution and the field of view needed for skin disease screening. The next step, they say, is to test how well it works in the clinic.

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Story Source:

The above story is based on materials provided by The Optical Society. Note: Materials may be edited for content and length.

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