Melanoma Dispatch
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Two Array-Invented MEK Inhibitors Showcased At ASCO

"Two Array BioPharma-invented MEK inhibitors, binimetinib (MEK162) and selumetinib, were showcased at the 50th annual meeting of the American Society of Clinical Oncology (ASCO).  At the meeting, preliminary data for the combination of binimetinib and CDK4/6 inhibitor LEE011 (discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals) from a Phase 1b/2 dose-escalation study conducted by Novartis in NRAS-mutant melanoma indicates the combination demonstrated an acceptable safety profile for most patients with promising preliminary antitumor activity.  Additionally, preliminary data for selumetinib showed favorable clinical activity in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs)."


Editor's note: This article discusses a melanoma treatment that combines two durgs: binimetinib (aka MEK162) and selumetinib. A clinical trial recently found that the combo shows promise for melanoma patients whose tumors have mutations in the NRAS gene, as detected by molecular testing. Binimetinib is also being tested as a potential treatment for patients whose tumors have mutations in the BRAF gene.

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Array BioPharma  |  Jun 2, 2014

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New Drug Overcomes Resistance to BRAF Inhibitors in Mice and Cultured Human Cells

An experimental drug may strengthen treatments that target melanomas with mutations in the BRAF gene, reported researchers from the pharmaceutical company Merck at the American Association for Cancer Research's 2013 meeting. Treatments that target BRAF often stop working because tumors activate a related protein called ERK, which is the target of Merck's new drug. Called SCH772984, the drug inhibits ERK in cultured human tumor cells with BRAF, NRAS, or KRAS mutations; slows cell division in human tumor cells that resist treatments that target BRAF or MEK; and shrinks tumors in mice. The researchers have begun a phase I clinical trial of an ERK inhibitor in people with tumors.

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American Association for Cancer Research│Apr 7, 2013

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First Treatment that Targets Melanomas with NRAS Mutations

A phase II study suggests that a MEK inhibitor drug benefits people who have melanomas with NRAS mutations, which currently have no targeted treatments. The drug, called MEK162, shrank tumors in 20% of NRAS-mutated melanoma patients (6 out of 30). MEK162 also shrank tumors in 20% of BRAF-mutated melanoma patients (8 out of 41), as well as tumors that had spread to the brain in two patients. This study is registered with ClinicalTrials.gov as number NCT01320085 and is now recruiting more patients with NRAS mutations.

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The Lancet Oncology │ Mar 2013

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SMURF2 Inhibitors Increase Effectiveness of MEK Inhibitors

Treatments that target a protein called MEK could work better when combined with drugs that inhibit a protein called SMURF2, according to research in the British Journal of the National Cancer Institute. MEK is involved in cell division and can be activated by BRAF and NRAS mutations. However, melanomas often resist MEK inhibitors. The researchers found that MEK inhibitors made melanoma cells grown in the laboratory produce too much of a protein called SMURF2. This in turn led to overproduction of another protein called MITF, which protects melanomas against MEK inhibitors. When treated with both a MEK inhibitor called selumetinib and a SMURF2 inhibitor, tumor growth was suppressed by 98% in mice.

 

Primary source: http://jnci.oxfordjournals.org/content/105/1/33.abstract?sid=76bd523d-0853-4b55-abe1-b7781898c5a3

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ScienceDaily | Dec 19, 2012

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Binimetinib Continues To Advance In Clinical Development

Binimetinib Continues To Advance In Clinical Development | Melanoma Dispatch | Scoop.it

"Three Phase 3 trials with binimetinib continue to enroll in advanced cancer patients:  NRAS-mutant melanoma (NEMO / NCT01763164), low-grade serous ovarian cancer (MILO / NCT01849874) and BRAF-mutant melanoma (COLUMBUS / NCT01909453).  NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing from the NRAS-mutant melanoma study estimated to be in 2015."


Editor's note: This is a press release from a company that is testing a new potential treatment for melanoma called binimetinib, or "MEK162." The drug is being tested in clinical trials (learn more about clinical trials). One of the trials is enrolling melanoma patients whose tumors have mutations in the NRAS gene, as detected by molecular testing. Another is enrolling patients with BRAF mutations.

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Array Biopharma  |  Apr 23, 2014

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BRAF Mutations Less Likely in Melanomas in Ireland

BRAF mutations, which are found in about half of melanomas, are far less common amongst Irish people, suggests a study presented at the American Association for Cancer Research's annual meeting. The researchers compared the melanomas of people in Ireland and Belgium and found that BRAF mutations occurred in only 21% of the former compared to the more typical 52% of the latter. This could be due to other genetic differences between the two countries. First, Irish patients had more NRAS mutations (21% vs 13%), which do not occur in melanomas with BRAF mutations. Second, 12% percent of the Irish patients had c-MET mutations, which are rare in melanomas, while none of the Belgian patients did. This work shows that treatments should be targeted to reflect genetic differences among populations.

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American Association for Cancer Research│Apr 7, 2013

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Combination Statin and Kinase Treatments Promising in Cultured Melanoma Cells

A new drug combination could treat melanomas that resist therapy with a single drug, suggests research that appeared in Cancer Discovery on melanoma cells grown in the laboratory. The researchers tested melanoma cells that had BRAF mutations and resisted treatment with the BRAF inhibitor vemurafenib, and that had NRAS mutations, which resist many treatments. The most effective combination treatment was statins, which are commonly used to treat high cholesterol, but can also kill melanoma cells, and drugs that inhibit proteins called cyclin-dependent kinases, which are involved in cell division.

 

Primary source: http://cancerdiscovery.aacrjournals.org/content/3/1/52.abstract?sid=6d6d2d16-9fee-4558-b7e4-72874b041917

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Dermatology Times | Dec 19, 2012

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Drug Targets Two Common Melanoma Mutations

An experimental drug could help control some melanomas that have BRAF or NRAS mutations, according to a report at an American Society of Clinical Oncology meeting. Tumors shrank or did not get worse in 8 out of 35 patients with the most common BRAF mutation (V600E), and in 6 out of 28 patients with NRAS mutations. This is the first targeted treatment for melanomas that have NRAS mutations. BRAF and NRAS mutations can activate a protein called MEK that is involved in cell division. The experimental drug, which is called MEK162, is a MEK inhibitor. The side effects of MEK162, which included diarrhea, rashes and swelling, were manageable.

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MedPage Today | Jun 8, 2012

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