{"id":776,"date":"2014-09-17T13:52:04","date_gmt":"2014-09-17T17:52:04","guid":{"rendered":"http:\/\/blogs.shu.edu\/cancer\/?p=776"},"modified":"2021-07-02T08:51:58","modified_gmt":"2021-07-02T12:51:58","slug":"selectively-targeting-metabolism-in-mitochondria-in-cancer-cells","status":"publish","type":"post","link":"http:\/\/blogs.shu.edu\/cancer\/2014\/09\/17\/selectively-targeting-metabolism-in-mitochondria-in-cancer-cells\/","title":{"rendered":"Selectively Targeting Metabolism in Mitochondria In Cancer Cells"},"content":{"rendered":"

An experimental drug, CPI-613, was shown to be safe and induce several responses in a Phase I study of patients with advanced refractory hematologic malignancies. The drug targets mitochondrial enzymes of cancer cells<\/a> and is not harmful to normal cells at therapeutic doses.<\/p>\n

One patient with Myelodysplastic Syndrome had a complete response<\/a> that has been durable for three years. Another patient had a partial response that has lasted for 2 years. In leukemia cell lines, Responses were observed in 29% of patients completing the treatment. \u00a0CPI-613 inhibited mitochondrial respiration<\/a>, consistent with its proposed mechanism of action.<\/p>\n

Based on the results of the Phase I study, a Phase II trial is underway at Wake Forrest University.<\/p>\n

How does it work, and why is it selective to cancer cells?<\/p>\n

CPI-613 is an analog of lipoic acid, which causes hyperphosphorylation and deactivation of the E1 Pyruvate Dehydrogenase<\/a> enzyme complex, which is essential to transforming pyruvate into Acetyl CoA. This effectively shuts down energy production in the mitochondria.<\/p>\n

\"14877443_130430_1814_23\"<\/a>

http:\/\/www.memrise.com\/course\/43238\/durham-university-medicine-year-one\/135\/<\/a><\/p><\/div>\n

Mitochrondria, which are the powerhouses of the cell, are used differently by\u00a0healthy cells<\/a>\u00a0and cancer cells. Healthy cells use mitochondria as a source of energy to carry out essential functions, whereas\u00a0leukemia cells<\/a>\u00a0use it to reproduce faster and to repair damage from chemotherapy. So, cancer cells are especially ore sensitive to PDH inhibition than are normal cells; that is the mechanism for the observed selectivity of CPI-613 in cancer cells versus normal cells in growth inhibition and apoptosis<\/p>\n

\"\"<\/a>

Cornerstone Pharmaceuticals – http:\/\/www.cornerstonepharma.com\/cancer-metabolism\/our-approach<\/a><\/p><\/div>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

An experimental drug, CPI-613, was shown to be safe and induce several responses in a Phase I study of patients with advanced refractory hematologic malignancies. The drug targets mitochondrial enzymes of cancer cells and is not harmful to normal cells at therapeutic doses.<\/p>\n","protected":false},"author":2252,"featured_media":394,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[428,36],"tags":[432,430,433,429,101,431],"class_list":["post-776","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cellular-metabolism","category-pharmacokinetics-pharmacodynamics","tag-cornerstone-pharmaceuticals","tag-cpi-613","tag-leukemia","tag-mitochondria","tag-myelodysplastic-syndrome","tag-pyruvate-dehudrogenase-e1-complex"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/776","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/users\/2252"}],"replies":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/comments?post=776"}],"version-history":[{"count":4,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/776\/revisions"}],"predecessor-version":[{"id":4996,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/posts\/776\/revisions\/4996"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/media\/394"}],"wp:attachment":[{"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/media?parent=776"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/categories?post=776"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/blogs.shu.edu\/cancer\/wp-json\/wp\/v2\/tags?post=776"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}