{"id":7481,"date":"2012-08-22T05:22:38","date_gmt":"2012-08-22T04:22:38","guid":{"rendered":"http:\/\/www.ilmelanoma.com\/?p=7481"},"modified":"2026-10-16T10:44:30","modified_gmt":"2026-10-16T09:44:30","slug":"elesclomol-role-melanoma","status":"publish","type":"post","link":"https:\/\/www.ilmelanoma.com\/en\/elesclomol-role-melanoma\/","title":{"rendered":"Elesclomol role in melanoma"},"content":{"rendered":"
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A laboratory study led by UNC medical oncologist\u00a0Stergios Moschos, MD, demonstrates how a new targeted drug, Elesclomol, blocks oxidative phosphorylation, which appears to play essential role in melanoma that has not been well-understood.\u00a0 Elesclomol (Synta Pharmaceuticals, Lexington, MA) was previously shown to have clinical benefit only in patients with normal serum lactate dehydrogenase (LDH), a laboratory test routinely used to assess activity of disease.\u00a0For more than 60 years, scientists have known that cancer cells undergo glycolysis, or metabolize glucose, at a much higher rate than normal cells.\u00a0 The observation, called the Warburg effect, demonstrated that the normal energy producing processes in the cell are disrupted in cancer cells, preventing them from using metabolic pathways in the cell\u2019s mitochondria (often called the cell\u2019s \u201cpower plants\u201d). \u00a0\u00a0Recently, however, increasing evidence suggests that, in addition to glycolysis, other metabolic pathways may also play a role in cancer, with important therapeutic implications. A promising strategy for targeting cancer cells, while sparing normal cells, is to target these altered metabolic processes with drug therapies.\u00a0 Elesclomol has been shown to trigger cell death in metastatic melanoma cells, primarily by suppressing oxidative phosphorylation \u2013 the process that cells use to transform nutrients into energy. \u00a0Moschos and his team demonstrated in the lab that metastatic melanoma cells exhibit a higher rate of glycolysis compared to their normal counterpart cells, termed melanocytes, which would be expected due to the Warburg effect. \u00a0\u00a0\u201cBut we also found, surprisingly, that these cells have higher rates of oxidative phosphorylation \u2013 they are producing energy through more than one pathway, which explains a lot about how the drug works,\u201d says Dr. Moschos.\u00a0He notes that this drug has an interesting history.\u00a0 In a 600-patient phase III clinical trial conducted almost 4 years ago, Elesclomol had clinical benefit in the subgroup of patients with normal serum LDH.\u00a0 However, the FDA discontinued the trial, because the Elesclomol in combination with another chemotherapeutic drug may have negative effects in patients with high serum LDH, which is associated with poorer patient outcomes in metastatic melanoma.\u00a0 At the time, very little was known about Elesclomol\u2019s mechanism of action \u2013 blocking oxidative phosphorylation. \u00a0\u00a0\u201cOur inability to show how Elesclomol worked through measurement of biomarkers was the major driver to conduct this laboratory study,\u201d said Moschos, whose team took the clinical trial results back to the lab to try to figure out why the drug worked. \u00a0\u201cOur results suggest that targeting oxidative phosphorylation in melanoma is a promising strategy for early metastatic disease, before melanoma cells switch their primary metabolic source to glycolysis, as Otto Warburg showed 60 years ago\u201d said Dr. Moschos.\u00a0\u201cSecond, we were able to demonstrate a mechanism of resistance to Elesclomol, where long-term exposure to the drug leads to the selection of melanoma cells with high levels of glycolysis.\u00a0 This suggests that a two-pronged strategy aimed at blocking both metabolic pathways may be called for.\u201d\u00a0The results of the study were published today in the journal Public Library of Science One.\u00a0Dr. Moschos conducted the research when he was a faculty member at the University of Pittsburgh Melanoma and Skin Cancer Program in collaboration with Dr. Bennett Van Houten, Richard M. Cyert Chair in Molecular Oncology, University of Pittsburgh.\u00a0 He joined UNC\u2019s division of hematology\/oncology and UNC Lineberger Comprehensive Cancer Center in January.\u00a0 The research appears today in Proceedings of the Library of Science ONE.\u00a0Other members of the research team include scientists from the University of Pittsburgh, the Women\u2019s Health Integrated Research Center at Inova Health System in Annandale, VA, Carnegie Mellon University and the University of Heidelberg.\u00a0The project was funded by a Career Development Award of a SPORE in Skin Cancer at the University of Pittsburgh (National Cancer Institute grant P50CA121973 ) and a Pennsylvania Department of Health PA CURE award.\u00a0 Synta Pharmaceuticals Corporation provided the Elesclomol drug used in the laboratory research.<\/p>\n

from: UNC Health Care<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

A laboratory study led by UNC medical oncologist\u00a0Stergios Moschos, MD, demonstrates how a new targeted drug, Elesclomol, blocks oxidative phosphorylation, which appears to play essential role in melanoma that has not been well-understood.\u00a0 Elesclomol (Synta Pharmaceuticals, Lexington, MA) was previously shown to have clinical benefit only in patients with normal serum lactate dehydrogenase (LDH), a […]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-7481","post","type-post","status-publish","format-standard","hentry","category-cura-melanoma"],"_links":{"self":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7481","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/comments?post=7481"}],"version-history":[{"count":1,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7481\/revisions"}],"predecessor-version":[{"id":10769,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/posts\/7481\/revisions\/10769"}],"wp:attachment":[{"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/media?parent=7481"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/categories?post=7481"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ilmelanoma.com\/en\/wp-json\/wp\/v2\/tags?post=7481"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}