Identification of a novel tyrosine kinase inhibitor for acute myeloid leukemia

March 17, 2016, Journal of Clinical Investigation

Acute myeloid leukemia (AML) is a cancer of myeloid stem cells that develops in both adult and pediatric populations. Mutations that cause hyperactivation of the FMS-like tyrosine kinase 3 (FLT3) are commonly found in AML, and several clinical trials are testing FLT3 inhibitors. However, resistance to FLT3 inhibitors can develop, highlighting the need for additional approaches to treating AML.

Douglas Graham of the University of Colorado and colleagues at the University of North Carolina and UCSF report in JCI Insight the development of a new drug that targets both resistant tumors and FLT3-independent AML. This research group previously documented that the receptor MERTK is elevated in the majority of acute leukemias.

They now show in culture and in preclinical models that the newly developed compound MRX-2843 exerts antitumor effects. Using a xenograft model in which patient-derived AML cells were injected into mice, they found that MRX-2843 treatment improved survival, even in cases of tumors resistant to the FLT3 inhibitor quizartinib.

Collectively, this study provides rationale for further exploring the clinical utility of MRX-2843.

Explore further: Phase I clinical trial of anti-cancer drug FF-10101 in patients with relapsed or refractory acute myeloid leukemia

More information: Katherine A. Minson et al. The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia, JCI Insight (2016). DOI: 10.1172/jci.insight.85630

Related Stories

Phase I clinical trial of anti-cancer drug FF-10101 in patients with relapsed or refractory acute myeloid leukemia

November 10, 2015
FUJIFILM Corporation today announced to conduct a clinical trial of its anti-cancer drug FF-10101 in patients with relapsed or refractory acute myeloid leukemia (AML) in the United States next year. FF-10101 is a new drug ...

A new target in acute myeloid leukemia

July 16, 2012
Acute myeloid leukemia, a common leukemia in adults, is characterized by aberrant proliferation of cancerous bone marrow cells. Activating mutations in a protein receptor known as FLT3 receptor are among the most prevalent ...

Experimental drug shows promise for treatment-resistant leukemias

April 8, 2014
Research in mice and human cell lines has identified an experimental compound dubbed TTT-3002 as potentially one of the most potent drugs available to block genetic mutations in cancer cells blamed for some forms of treatment-resistant ...

Opening the door to the cause of myeloid leukemia: Finding the targets of common mutation

July 23, 2015
Researchers at the University of Birmingham have made a breakthrough in understanding how mutated genes in leukaemia reprogram blood stem cells and send them spiralling out of control.

Inducing metabolic catastrophe in cancer cells

August 31, 2015
A study published in The Journal of Cell Biology describes a way to force cancer cells to destroy a key metabolic enzyme they need to survive.

Normal enzyme aids a mutant one to fuel blood cancer's growth

February 10, 2014
Reinforcing the need to look beyond genomic alterations to understand the complexity of cancer, researchers from Dana-Farber/Boston Children's Cancer and Blood Disorders Center report that a normal enzyme called SYK pairs ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.