Overcoming the impasse in acute myeloid leukemia research

AML drug combination figure

A heat map by Kurtz et al. comparing the sensitivities of leukemia cells to drug combinations.

Nine drug companies and six universities have now joined an unusual collaboration to break the logjam in research on acute myeloid leukemia (AML), a blood cancer lacking effective treatments. Less than 25 percent of newly diagnosed patients survive beyond five years with a standard of care based on 40-year-old chemotherapy agents.

The research initiative, Beat AML, is supplying a stock of drug candidates and treatment ideas, a dozen of which were presented on Dec. 5-8 at the American Society of Hematology Annual Meeting in Orlando, Florida.

Beat AML is zeroing in on potential drivers of the disease by sequencing cancer cell DNA from hundreds of patients who volunteer samples. In the two years since the Beat AML initiative was launched by The Leukemia & Lymphoma Society and the Knight Cancer Institute at Oregon Health & Science University, researchers have collected more than 450 samples. Investigators have identified more than 10 cell signaling pathways and mutations that are potentially playing a role in disease progression.

“With the wide range of collaborators now involved in Beat AML, we are able to better explore innovative ideas for targeting the many drivers of this disease,” Knight Cancer biologist Jeffrey Tyner, Ph.D., said in a news release. Tyner leads the initiative’s industry collaborations. “Integration of our strong drug-screening pipeline with the large amounts of genomic data being generated is allowing us to make great strides in understanding the connections between tumor genotype and drug response.”

Among the Beat AML findings presented at the ASH meeting:

  • Using a unique method to test drugs used together, Knight Cancer Institute researcher Stephen Kurtz, Ph.D., colleagues, identified drug combinations that are highly active against leukemia cells in specific patients. The next step is to link these findings with the gene alterations that make cancer cells sensitive to the drug combinations, and use those results to design clinical trials. (Abstract 865)
  • Disrupting the cancer cell microenvironment shows promise as a new path to target AML. A particular type of immune cell supports the growth of AML cells, and two studies to be presented by Knight Cancer Institute researchers show that depleting these immune cells with a targeted agent eliminates the supportive environment, causing leukemia cells to die. (Abstracts 3824 and 4439)
  • Targeting a key inflammatory pathway offers a new therapeutic approach that could benefit AML patients. A Knight Cancer Institute team led by Anupriya Agarwal, Ph.D., found that increased secretion of pro-inflammatory cytokines in the microenvironment of leukemia cells drives disease progression in AML, and showed that blocking this signaling inhibits cancer cell growth. (Abstracts 570, 866 and 2603)

Aptose Biosciences and Constellation Pharmaceuticals were among the first industry collaborators. Others include argenx, AstraZeneca, Genentech, Janssen Research & Development LLC, Seattle Genetics and Takeda Pharmaceuticals International Co. The Academic collaborators are with the Huntsman Cancer Institute at the University of Utah, Stanford University, Sylvester Comprehensive Cancer Center at the University of Miami, UT Southwestern Medical Center and the University of Colorado Cancer Center.

The idea for the industry-academic collaboration came together in 2012 when The Leukemia & Lymphoma Society asked Knight Cancer Institute Director Brian Druker, M.D., and colleagues if they could come up with a research plan to “do for AML what you’ve done for CML,” that is, find a path to treatments as effective as Gleevec, the drug for chronic myeloid leukemia that converted the fatal cancer into a manageable chronic condition. The society committed $8.2 million to fund the plan devised by Druker’s team.

 

 

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Comments

  1. Kudos to OCTRI for helping create the database used by AML researchers! (OCTRI is supported by NIH ULTR000128 Clinical Translational Science Award.)

About the Author

Joe worked as a cell biology researcher at the Rockefeller University in New York City until he figured out he could make a living writing about science for newspapers and magazines. He's been a science writer with the OHSU Knight Cancer Institute since September 2015.

Targeting leukemia with drug combinations

Targeting leukemia with drug combinations

Cancer researchers have devised a way to rapidly screen combinations of drugs to identify pairs of agents most likely to work synergistically against some of the most difficult to treat forms of leukemia.