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Precision Oncology: Creating a Genomic Guide for Melanoma Therapy

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Melanoma cell

Caption: Human malignant melanoma cell viewed through a fluorescent, laser-scanning confocal microscope. Invasive structures involved in metastasis appear as greenish-yellow dots, while actin (green) and vinculin (red) are components of the cell’s cytoskeleton.
Credit: Vira V. Artym, National Institute of Dental and Craniofacial Research, NIH

It’s still the case in most medical care systems that cancers are classified mainly by the type of tissue or part of the body in which they arose—lung, brain, breast, colon, pancreas, and so on. But a radical change is underway. Thanks to advances in scientific knowledge and DNA sequencing technology, researchers are identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that arise in totally different parts of the body can sometimes have a lot in common. Not only can molecular analysis refine diagnosis and provide new insights into what’s driving the growth of a specific tumor, it may also point to the treatment strategy with the greatest chance of helping a particular patient.

The latest cancer to undergo such rigorous, comprehensive molecular analysis is malignant melanoma. While melanoma can rarely arise in the eye and a few other parts of the body, this report focused on the more familiar “cutaneous melanoma,” a deadly and increasingly common form of skin cancer [1].  Reporting in the journal Cell [2], The Cancer Genome Atlas (TCGA) Network says it has identified four distinct molecular subtypes of melanoma. In addition, the NIH-funded network identified an immune signature that spans all four subtypes. Together, these achievements establish a much-needed framework that may guide decisions about which targeted drug, immunotherapy, or combination of therapies to try in an individual with melanoma.


Knocking Out Melanoma: Does This Triple Combo Have What It Takes?

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3-Way Knockout of MelanomaIt would be great if we could knock out cancer with a single punch. But the more we learn about cancer’s molecular complexities and the immune system’s response to tumors, the more it appears that we may need a precise combination of blows to defeat a patient’s cancer permanently, with no need for a later rematch. One cancer that provides us with a ringside seat on the powerful potential—and tough challenges—of targeted combination therapy is melanoma, especially the approximately 50% of advanced tumors with a specific “driver” mutation in the BRAF gene [1].

Drugs that target cells carrying BRAF mutations initially provided great hope for melanoma, with many reports of dramatic shrinkage of tumors in patients with advanced disease.  But almost invariably, the disease recurred and was no longer responsive to those same drugs.  A few years ago, researchers thought they’d come up with a solid combination to fight BRAF-mutant melanoma: a one-two punch that paired a BRAF-inhibiting drug with an agent that sensitized the immune system [2]. However, when that combo was tested in humans, the clinical trial had to be stopped early because of serious liver toxicity [3]. Now, in a mouse study published in Science Translational Medicine, NIH-funded researchers at the University of California, Los Angeles (UCLA) provide renewed hope for a safe, effective combination therapy for melanoma—with a strategy that adds a third drug to the mix [4].


Lessons from a High School Student: Motivation + Perseverance = Success

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Emily Ashkin Video

It may surprise you to learn that the poised young woman featured in this video was a sophomore in high school at the time the film was made. Today, Emily Ashkin is a high school senior with impressive laboratory experience and science awards to her name.  As it happens, she’s also introducing me when I deliver a keynote address at the Melanoma Research Alliance’s annual scientific meeting — today, here in Washington, D.C.

What struck me most when I heard Emily’s story was her fearlessness. When mentoring young students, helping some to believe in themselves can be a real challenge. Not Emily. She faces her challenges by seeking solutions, asking—as she does in the video—“Why can’t that be me?”


Personalized Cancer Vaccine Enters Human Trials

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Photo of a researcher looking at a silver disc held by a curved hemostat

Caption: The new melanoma vaccine, which is implanted beneath the skin, is now being tested in human trials.
Credit: Wyss Institute and Amos Chan

This aspirin-sized disk is the first therapeutic cancer vaccine implanted beneath the skin [1]. We know it can eradicate melanoma in mice—the deadliest form of skin cancer—with impressive efficacy [2]. Now, it’s being tested in human trials.


Why Redheads Are More Susceptible to Melanoma

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Redheaded girl on a beachWe’ve long known that redheads are 10 to 100 times more vulnerable than people with other hair colors to melanoma, a particularly dangerous form of skin cancer. What we haven’t known is why. Why would the hue of your hair have anything to do with your cancer risk? When you consider that melanoma is our most deadly form of skin cancer— expected to cause some 77,000 cases and 9,400 deaths this year alone—it’s important to figure out the connection. A new study [1], led by NIH-funded researchers in Boston, has identified a couple of key links.


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