{"id":46134,"date":"2017-10-15T10:03:11","date_gmt":"2017-10-15T17:03:11","guid":{"rendered":"http:\/\/69.46.6.243\/?p=46134"},"modified":"2017-10-15T10:03:35","modified_gmt":"2017-10-15T17:03:35","slug":"novel-treatment-causes-cancer-to-self-destruct-without-affecting-healthy-cells","status":"publish","type":"post","link":"https:\/\/new.thepinetree.net\/?p=46134","title":{"rendered":"Novel Treatment Causes Cancer to Self-Destruct Without Affecting Healthy Cells"},"content":{"rendered":"<p>Bronx, NY&#8230;Scientists at\u00a0<a href=\"http:\/\/www.einstein.yu.edu\/\">Albert Einstein College of Medicine<\/a>\u00a0have discovered the first compound that directly makes cancer cells commit suicide while sparing healthy cells. The new treatment approach, described in today\u2019s issue of\u00a0<a href=\"https:\/\/authors.elsevier.com\/a\/1VsIc5TA51HrHP\" target=\"_blank\" rel=\"noopener\"><em>Cancer Cell<\/em><\/a>, was directed against acute myeloid leukemia (AML) cells but may also have potential for attacking other types of cancers.<\/p>\n<p><iframe loading=\"lazy\" width=\"640\" height=\"360\" src=\"https:\/\/www.youtube.com\/embed\/5Mc-waVRPeA\" frameborder=\"0\" allowfullscreen><\/iframe><\/p>\n<p><span class=\"imgBorderLeftTop threehundred\"><img decoding=\"async\" src=\"http:\/\/www.einstein.yu.edu\/images\/dynamichomeimages\/fullstoryimages\/evripidis-gavathiotis-wide-angle.jpg\" alt=\"Researchers, led by Evripidis Gavathiotis, Ph.D., at Albert Einstein College of Medicine have discovered the first compound that directly makes cancer cells commit suicide while sparing healthy cells.\" width=\"300\" \/><br \/>\nEvripidis Gavathiotis, Ph.D.<\/span>\u201cWe\u2019re hopeful that the targeted compounds we\u2019re developing will prove more effective than current anti-cancer therapies by directly causing cancer cells to self-destruct,\u201d says\u00a0<a href=\"http:\/\/www.einstein.yu.edu\/faculty\/12958\/evripidis-gavathiotis\/\">Evripidis Gavathiotis, Ph.D.<\/a>, associate professor of\u00a0<a href=\"http:\/\/www.einstein.yu.edu\/departments\/biochemistry\/\">biochemistry<\/a>\u00a0and of\u00a0<a href=\"http:\/\/www.einstein.yu.edu\/departments\/medicine\/\">medicine<\/a>\u00a0and senior author of the study. \u201cIdeally, our compounds would be combined with other treatments to kill cancer cells faster and more efficiently\u2014and with fewer adverse effects, which are an all-too-common problem with standard chemotherapies.\u201d<\/p>\n<p>AML accounts for nearly one-third of all new leukemia cases and kills more than 10,000 Americans each year. The survival rate for patients has remained at about 30 percent for several decades, so better treatments are urgently needed.<\/p>\n<p>The newly discovered compound combats cancer by triggering apoptosis\u2014an important process that rids the body of unwanted or malfunctioning cells. Apoptosis trims excess tissue during embryonic development, for example, and some chemotherapy drugs indirectly induce apoptosis by damaging DNA in cancer cells.<\/p>\n<p>Apoptosis occurs when BAX\u2014the \u201cexecutioner protein\u201d in cells\u2014is activated by \u201cpro-apoptotic\u201d proteins in the cell. Once activated, BAX molecules home in on and punch lethal holes in mitochondria, the parts of cells that produce energy. But all too often, cancer cells manage to prevent BAX from killing them. They ensure their survival by producing copious amounts of \u201canti-apoptotic\u201d proteins that suppress BAX and the proteins that activate it.<\/p>\n<p><span class=\"imgNoBorderRightTop threefifty\"><iframe loading=\"lazy\" src=\"https:\/\/www.youtube.com\/embed\/5Mc-waVRPeA?rel=0&amp;showinfo=0&amp;autohide=1\" width=\"350\" height=\"196.875\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\" data-fullscreen=\"true\" data-mce-fragment=\"1\"><\/iframe><br \/>\nThis image depicts the structure of the BAX protein (purple). The activator compound BTSA1 (orange) has bound to the active site of BAX (green), changing the shape of the BAX molecule at several points (shown in yellow, magenta and cyan). BAX, once in its final activated form, can home in on mitochondria and puncture their outer membranes, triggering apoptosis (cell death).<\/span><\/p>\n<p>\u201cOur novel compound revives suppressed BAX molecules in cancer cells by binding with high affinity to BAX\u2019s activation site,\u201d says Dr. Gavathiotis. \u201cBAX can then swing into action, killing cancer cells while leaving healthy cells unscathed.\u201d<\/p>\n<p>Dr. Gavathiotis was the lead author of a\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v455\/n7216\/full\/nature07396.html?foxtrotcallback=true\" target=\"_blank\" rel=\"noopener\">2008 paper in\u00a0<em>Nature<\/em><\/a>\u00a0that first described the structure and shape of BAX\u2019s activation site. He has since looked for small molecules that can activate BAX strongly enough to overcome cancer cells\u2019 resistance to apoptosis. His team initially used computers to screen more than one million compounds to reveal those with BAX-binding potential. The most promising 500 compounds\u2014many of them newly synthesized by Dr. Gavathiotis\u2019 team\u2014were then evaluated in the laboratory.<\/p>\n<p>\u201cA compound dubbed BTSA1 (short for BAX Trigger Site Activator 1) proved to be the most potent BAX activator, causing rapid and extensive apoptosis when added to several different human AML cell lines,\u201d says lead author Denis Reyna, M.S., a doctoral student in Dr. Gavathiotis\u2019 lab. The researchers next tested BTSA1 in blood samples from patients with high-risk AML. Strikingly, BTSA1 induced apoptosis in the patients\u2019 AML cells but did not affect patients\u2019 healthy blood-forming stem cells.<\/p>\n<blockquote id=\"pullquote\"><p>\u201cWe\u2019re hopeful that the targeted compounds we\u2019re developing will prove more effective than current anti-cancer therapies by directly causing cancer cells to self-destruct.\u201d<\/p>\n<p><cite>\u2013 Evripidis Gavathiotis, Ph.D.<\/cite><\/p><\/blockquote>\n<p>Finally, the researchers generated animal models of AML by grafting human AML cells into mice. BTSA1 was given to half the AML mice while the other half served as controls. On average, the BTSA1-treated mice survived significantly longer (55 days) than the control mice (40 days), with 43 percent of BTSA1-treated AML mice alive after 60 days and showing no signs of AML.<\/p>\n<p>Importantly, the mice treated with BTSA1 showed no evidence of toxicity. \u201cBTSA1 activates BAX and causes apoptosis in AML cells while sparing healthy cells and tissues\u2014probably because the cancer cells are primed for apoptosis,\u201d says Dr. Gavathiotis. He notes that his study found that AML cells from patients contained significantly higher BAX levels compared with normal blood cells from healthy people. \u201cWith more BAX available in AML cells,\u201d he explained, \u201ceven low BTSA1 doses will trigger enough BAX activation to cause apoptotic death, while sparing healthy cells that contain low levels of BAX or none at all.\u201d<\/p>\n<p>Plans call for Dr. Gavathiotis and his team to see whether BTSA1 will show similar effectiveness when tested on animal models of other types of cancer.<\/p>\n<p>The paper, \u201cDirect activation of BAX by BTSA1 overcomes apoptosis resistance in acute myeloid leukemia,\u201d was published October 9 in\u00a0<em>Cancer Cell<\/em>. In addition to Dr. Gavathiotis and Mr. Reyna, other Einstein researchers involved in the study were Thomas P. Garner, Ph.D., Andrea Lopez, M.S., Felix Kopp, Ph.D., Gaurav S. Choudhary, Ph.D., Ashwin Sridharan, M.D., Swathi-Rao Narayanagari, M.S., Kelly Mitchell, M.S., Baoxia Dong, Ph.D., Boris A. Bartholdy, Ph.D., Amit Verma, MB.B.S., and Ulrich Steidl, M.D., Ph.D.<\/p>\n<p>Funding for this research was provided by the National Cancer Institute (NCI), part of the National Institutes of Health (R01CA178394), and awards from the Sidney Kimmel Foundation for Cancer Research, the Gabrielle\u2019s Angels Foundation for Cancer Research, and the Pershing Square Sohn Cancer Research Alliance. Partial support was also provided by the Albert Einstein Cancer Center, which is funded by the NCI (P30CA013330).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Bronx, NY&#8230;Scientists at\u00a0Albert Einstein College of Medicine\u00a0have discovered the first compound that directly makes cancer cells commit suicide while sparing healthy cells. The new treatment approach, described in today\u2019s issue of\u00a0Cancer Cell, was directed against acute myeloid leukemia (AML) cells but may also have potential for attacking other types of cancers. Evripidis Gavathiotis, Ph.D.\u201cWe\u2019re hopeful [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":46139,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_cbd_carousel_blocks":"[]","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[20,33,1],"tags":[],"class_list":["post-46134","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-featured","category-health-fitness","category-news","last_archivepost"],"jetpack_featured_media_url":"https:\/\/new.thepinetree.net\/wp-content\/uploads\/2017\/10\/New-Treatment-Causes-Cancer-to-Self-Destruct.jpg","jetpack_sharing_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/46134","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=46134"}],"version-history":[{"count":0,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/46134\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/media\/46139"}],"wp:attachment":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=46134"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=46134"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=46134"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}