{"id":25049,"date":"2019-06-25T09:16:42","date_gmt":"2019-06-25T15:16:42","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=25049"},"modified":"2022-08-18T08:04:25","modified_gmt":"2022-08-18T14:04:25","slug":"new-leukemia-drug-points-to-new-front-in-fight-against-cancer","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/new-leukemia-drug-points-to-new-front-in-fight-against-cancer\/","title":{"rendered":"New leukemia drug points to new front in fight against cancer"},"content":{"rendered":"
<\/div>

Often, you don\u2019t have to know how something works \u2013 what\u2019s important is that<\/em> it works. Few of us are versed in the chemical reactions involved in the transformation of chocolate chip cookie dough into a nice, gooey batch, after all.<\/p>\n

\"purple-colored
A micrograph of acute myeloid leukemia cells. (Getty Images)<\/figcaption><\/figure>\n

But that\u2019s not how it usually goes in cancer medicine, where scientists have delved into the inner workings of cells to understand the ways in which cancer outfoxes the body\u2019s natural defenses.<\/p>\n

Let’s delve in a new leukemia drug<\/strong><\/h3>\n

They did such delving for a drug called venetoclax<\/a> as related to\u00a0chronic lymphocytic lymphoma (CLL<\/a>), the most common type of leukemia. They found that venetoclax worked by blocking a protein that CLL cancer cells generate and exploit to stop a process called apoptosis, which would otherwise trigger the cancer cells to die.<\/p>\n

Venetoclax \u00a0also seemed to be effective in another type of leukemia \u2013 acute myeloid leukemia, or AML<\/a>, a nasty blood cancer that strikes mainly the elderly. Scientists assumed the drug worked the same way in AML as it did in CLL. What works for a chocolate chip cookie should work for a sugar cookie, after all.<\/p>\n

It took a University of Colorado School of Medicine team and a clinical trial at UCHealth University of Colorado Hospital<\/a> at the Anschutz Medical Campus (UCH) to demonstrate otherwise \u2013 and open up a promising new avenue in how we treat leukemia<\/a>. In the process, the team showed that a combination of venetoclax and low-dose chemotherapy starkly improves the prospects of those with AML. The FDA agreed, approving the drug for AML in November 2018.<\/p>\n

Journal club<\/strong><\/h3>\n
\"doctor
Dr. Daniel Pollyea takes promising lab work to patients in clinical trials at UCHealth.<\/figcaption><\/figure>\n

The story starts more than a decade ago, when Dr. Daniel Pollyea<\/a> was doing his fellowship in hematology and oncology at Stanford University. Fellows were expected to pick out a journal article, digest it, and summarize it for faculty during a \u201cjournal club.\u201d<\/p>\n

\u201cYou had to stand up there, present an article, and then get pummeled with questions and criticism,\u201d Pollyea said. \u201cSo you had to know that paper as well as any paper you\u2019d ever read before.\u201d<\/p>\n

Pollyea chose a paper by a team led by Craig T. Jordan, a PhD cancer biologist and, as Pollyea described him, \u201cone of the world\u2019s top experts on leukemia stem cells.\u201d Jordan was at the University of Rochester at the time.<\/p>\n

Not forgotten<\/strong><\/h3>\n

In 2011, Pollyea came to the CU School of Medicine, where he\u2019s now director of Leukemia Services and sees patients at UCH. A couple of years later, Jordan joined the CU faculty, where he\u2019s now chief of the Division of Hematology.<\/p>\n

Pollyea hadn\u2019t forgotten that journal article and had continued to follow Jordan\u2019s work. He sat down with Jordan and they agreed to build CU into the world\u2019s top authority on the biology of leukemia stem cells. They would get there by combining the work of Jordan\u2019s lab with clinical trials to translate lab discoveries into treatments for patients. Pollyea would lead those trials, with funding from the Leukemia & Lymphoma Society<\/a> providing key support (during the 2019 baseball season, Colorado Rockies\u2019 home runs landing on UCHealth\u2019s \u201cHit the Mitt for Charity<\/a>\u201d sign in Coors Field\u2019s left-field stands benefit the society).<\/p>\n

\u201cThe leukemia stem cell population is the root cause of AML and the source of relapse,\u201d Pollyea said, adding that killing AML stem cells would be \u201cakin to pulling the root up with the weed. You could actually eradicate the disease and not just stun it.\u201d<\/p>\n

Chink in the armor<\/strong><\/h3>\n

Jordan\u2019s lab had found something surprising with venetoclax. As Pollyea described it, venetoclax caused the AML stem cells to more or less starve to death<\/a>. The sugar cookie was in fact different than the chocolate chip cookie.<\/p>\n

Normal cells can burn different types of fuel, depending on what\u2019s available \u2013 sugar, fat, or the amino acids broken down from proteins. AML stem cells, Jordan\u2019s team found, run only on protein \u2013 and they showed, for the first time, that venetoclax stops protein metabolism in those stem cells. So in addition to chemotherapy, which uses chemicals to kill cancer cells as well as healthy cells; and immunotherapy, which uncloaks cancer cells so the immune system can attack them; the CU School of Medicine team discovered what looks to be a unique general approach to killing cancer. Call it starve-the-stem-cells therapy.<\/p>\n

Studying the new leukemia drug<\/strong><\/h3>\n
\"portrait\"
Craig T. Jordan, PhD, found venetoclax to work differently in acute myeloid leukemia stem cells, opening up a promising new avenue in the cancer fight.<\/figcaption><\/figure>\n

A clinical trial Pollyea led bore that out<\/a> with patients. The drug took effect quickly, and 67 percent of the 145 patients involved went into remission, with median survival of more than 17 months. (Only about 20 percent of patients only on the accompanying chemotherapy \u2013 the standard treatment \u2013 go into remission, and median survival is less than a year).<\/p>\n

Jordan and Pollyea continue to work on new recipes, as it were. The FDA\u2019s November 2018 approval<\/a> of venetoclax for AML was limited to patients ages 75 and over. New studies now happening at UCHealth \u2013 and only at UCHealth \u2013 aim to change that. One of them considers patients 60 and over<\/a>; the other is for patients as young as 18<\/a>.<\/p>\n

\u201cIt\u2019s the only setting in the world where a younger patient would be allowed not to receive standard intensive chemotherapy,\u201d Pollyea said.<\/p>\n

Funding the future<\/strong><\/h3>\n

The Leukemia & Lymphoma Society is helping support both new studies.<\/p>\n

\u201cLLS is our critical partner,\u201d Pollyea said. \u201cThey are just an incredible funding agency that really understands the science and I think recognizes the best approaches \u2013 the most novel and sometimes the riskiest approaches \u2013 that may not have any other funding source.\u201d<\/p>\n

A combination of medical creativity and high-risk, high-reward funding is just what it will take to tackle blood cancers that are anything but cookie-cutter.<\/p>\n","protected":false},"excerpt":{"rendered":"

Often, you don\u2019t have to know how something works \u2013 what\u2019s important is that it works. Few of us are versed in the chemical reactions involved in the transformation of chocolate chip cookie dough into a nice, gooey batch, after all. But that\u2019s not how it usually goes in cancer medicine, where scientists have delved […]<\/p>\n","protected":false},"author":23,"featured_media":25106,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[8],"tags":[1024,28,2563,63,4781],"class_list":["post-25049","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-blood-disorders-disease-care-hematology","tag-cancer-care-oncology","tag-leukemia","tag-pharmacy","tag-research-in-health-care"],"acf":[],"yoast_head":"\nNew leukemia drug a new front in fight against cancer - 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