{"id":25464,"date":"2015-11-02T12:04:41","date_gmt":"2015-11-02T17:04:41","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm\/?p=25464"},"modified":"2015-11-02T12:04:41","modified_gmt":"2015-11-02T17:04:41","slug":"unraveling-melanomas-mysteries-2","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2015\/11\/02\/unraveling-melanomas-mysteries-2\/","title":{"rendered":"Unraveling Melanoma\u2019s Mysteries"},"content":{"rendered":"

MED\u2019s Anurag Singh wins grant to study gene in deadly skin cancer<\/h4>\n
\"Anurag
Anurag Singh, a MED assistant professor, studies NRAS in melanoma with a three-year grant from the Melanoma Research Alliance. Photo by Mike Spencer<\/figcaption><\/figure>\n

Skin cancer is the most common of all cancers, with about 3.5 million cases diagnosed in the United States each year, according to the American Cancer Society<\/a>. And while melanoma is one of the least common types, representing only about 2 percent of skin cancer cases, it is one of the most deadly. Melanoma is so aggressive that doctors measure the tumor depth under a microscope\u2014the variance of a fraction of a millimeter may make the difference between survival and death.<\/p>\n

Knowledge about this disease has taken off since 2002, when scientists discovered tumor-inducing mutations in the BRAF gene in over 50 percent of melanoma cases. Drugs that target mutant BRAF, along with new therapies that boost a patient\u2019s immune system, have given doctors and patients hope, but treatments are still only partially effective. \u201cCancer is really smart,\u201d says Rhoda M. Alani<\/a>, the School of Medicine\u2019s Herbert Mescon Professor and Chair of dermatology. \u201cPatients respond to treatment, but then the cancer becomes resistant. We can make the cancer go away with targeted therapies, but it almost always comes back.\u201d<\/p>\n

In addition, says Alani, some forms of melanoma have no targeted therapy at all. About 20 percent of melanomas have a mutated gene called NRAS. These types of melanomas have no effective targeted treatment to date. That\u2019s where Anurag Singh<\/a> comes in.<\/p>\n

Singh, a MED assistant professor of pharmacology and medicine, is tackling this poorly understood melanoma by investigating how NRAS transforms healthy, normal skin cells into aggressive cancerous cells. The work is funded by a three-year, $150,000 grant from the Melanoma Research Alliance<\/a>.<\/p>\n

RAS genes\u2014named for \u201crat sarcoma\u201d because that\u2019s where scientists first found them\u2014belong to a family of molecules called G proteins, which are important for much signaling within human cells. There are about 200 G proteins of various shapes and sizes, but they all have one thing in common: they can become activated and then, after some period of time, automatically turn themselves off.<\/p>\n

Mutant forms of RAS have a problem: they can turn on, but they can\u2019t turn off. The mutant RAS is always on, always signaling, even when other signals order it to cease and desist. This nonstop signaling can lead to different effects: sometimes it makes a cell multiply uncontrollably, sometimes it prevents a cancer cell from self-destructing. This makes the mutant forms of RAS common in cancer, but scientists still don\u2019t know exactly how the mutations lead to disease.<\/p>\n

\u201cThe RAS mutation itself is not sufficient to cause a full-blown tumor,\u201d says Singh. \u201cIt creates a vulnerable state that can progress to a malignant state.\u201d<\/p>\n

Singh\u2019s lab studies how two forms of the RAS gene, NRAS and KRAS, interact and cooperate with other genes to form gene networks, analogous to computer circuits. The RAS mutations prevalent in melanoma also appear in pancreatic and colon cancer. Singh has already discovered that melanomas with NRAS mutations come in at least two different flavors. \u201cWe have identified two major types of NRAS networks in melanoma,\u201d he says. \u201cWe hypothesize that these subtypes can be treated with selective targeted anticancer agents or precision medicines. We hope to pinpoint vulnerabilities that can be blocked with chemotherapy.\u201d<\/p>\n

\u201cSingh\u2019s work is fundamental, basic science, but he has a strong interest in translational research,\u201d says Alani. \u201cIt\u2019s important to collaborate with physicians and think about specific applications, especially at a research institution like MED.\u201d<\/p>\n

While much of Singh\u2019s work looks at signals within an individual cell, he\u2019s also interested in how cells communicate with each other. \u201cI\u2019d like to study how an oncogene such as RAS regulates the tumor\u2019s microenvironment, and how that might affect interactions with the surrounding cells,\u201d he says. This network communications map\u00a0could provide valuable clues to how cancers grow and survive, and how medicine might be able to fight them.<\/p>\n

\u201cThat\u2019s what I think about: how can we effectively treat patients with mutations in the RAS genes,\u201d Singh says. \u201cUltimately, we\u2019re all in the business of trying to advance therapeutics to benefit patients.\u201d<\/p>\n

This BU Today<\/em> story was written by Barbara Moran<\/a>. A version of this article originally appeared on BU Research<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

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