Navigation Links
Experimental drug shows promise for treatment-resistant leukemias
Date:4/8/2014

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 leukemia.

Results of the research by Johns Hopkins Kimmel Cancer Center investigators, described March 6 in the journal Blood, show that two doses a day of TTT-3002 eliminated leukemia cells in a group of mice within 10 days. The treatment performed as well as or better than similar drugs in head-to-head comparisons.

More than 35 percent of acute myeloid leukemia (AML) patients harbor a mutation in the gene FMS-like tyrosine kinase-3 (FLT3). Normal FLT3 genes produce an enzyme that signals bone marrow stem cells to divide and replenish. But when FLT3 is mutated in some AML patients, the enzyme stays on permanently, causing rapid growth of leukemia cells and making the condition likely to relapse after treatment.

Many investigators are developing and testing drugs designed to block the FLT3 enzyme's proliferation, several of which are now in clinical trials. So far, their effectiveness has been limited, according to Donald Small, M.D., Ph.D., the Kyle Haydock Professor of Oncology and director of pediatric oncology at Johns Hopkins. Small led a team of researchers who originally cloned the FLT3 gene and linked it to leukemia a decade ago.

"We're very excited about TTT-3002, because it appears in our tests so far to be the most potent FLT3 inhibitor to date," says Small. "It showed activity against FLT3-mutated cells taken from patients and with minimal toxicity to normal bone marrow cells, making it a promising new candidate for the treatment of AML."

In a series of experiments with the drug, Small, postdoctoral fellow Hayley Ma, Ph.D., and others found that the amount of TTT-3002 needed to block FLT3 activity in human leukemia cell lines was six- to sevenfold lower than for the most potent inhibitor currently in clinical trials. TTT-3002 also inhibited proteins made by genes further down the FLT3 signaling pathway, including STAT5, AKT and MAPK, and showed activity against the most frequently occurring FLT3 mutations, FLT3/ITD and FLT3/D835Y. Many cancer drugs are currently ineffective against FLT3/D835Y mutations.

When the Johns Hopkins team tested the drug in a mouse model of leukemia, they found that it not only eliminated the presence of leukemic cells within 10 days of treatment but also that the mice lived an average of more than 100 days following treatment, to study completion, and resumed normal bone marrow activity. By contrast, mice treated with a placebo died an average of 18 days following treatment.

Additional studies found that TTT-3002 performed as well as sorafenib, another FLT3 inhibitor, in treating leukemic mice, and that the drug was toxic to leukemia cell samples taken from newly diagnosed and relapsed patients with AML but did not affect normal bone marrow cells taken from healthy donors.

A single dose of the medication caused more than 90 percent inhibition against FLT3 signaling that lasted for 12 hours, Small says.


'/>"/>

Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine
Source:Eurekalert

Related medicine news :

1. Diabetes drug shows promise in reducing Alzheimers disease in an experimental model
2. Experimental drug could enhance multiple myeloma and myeloid leukemia therapies
3. Experimental drug shows encouraging results in treating most common form of lung cancer
4. Studies of experimental hepatitis C drug show promise for preventing recurrence in liver transplant
5. ASSURE study of experimental agent to raise HDL yields disappointing and surprising results
6. York physicists offer novel insight into experimental cancer treatment
7. Experimental Drug Shows Benefits Against Melanoma in Early Study
8. Experimental Drugs Show Promise Against Prostate Cancer
9. Experimental Drug Seems to Aid Memory in Mice With Alzheimers
10. Mayo Clinic finds experimental drug inhibits growth in all stages of common kidney cancer
11. Experimental Drug for Hepatitis C Promising, Studies Show
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... 25, 2016 , ... Conventional wisdom preaches the benefits of moderation, whether it’s ... setting the bar too high can result in disappointment, perhaps even self-loathing. However, those ... goal. , Research from PsychTests.com reveals that behind the tendency to ...
(Date:6/24/2016)... ... June 24, 2016 , ... Marcy was in a crisis. Her son James, eight, was out ... family verbally and physically. , “When something upset him, he couldn’t control his emotions,” remembers ... would throw rocks at my other children and say he was going to kill them. ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San ... Society and the Road To Recovery® program to drive cancer patients to and from ... adults to ensure the highest quality of life and ongoing independence. Getting to ...
(Date:6/24/2016)... New York, NY (PRWEB) , ... June 24, ... ... lifestyle publication Haute Living, is proud to recognize Dr. Barry M. Weintraub as ... believes that “the most beautiful women in the world, and the most handsome ...
(Date:6/24/2016)... ... ... Venture Construction Group (VCG) sponsors Luke’s Wings 5th Annual ... Country Club at 1201 Rockville Pike, Rockville, Maryland, 20852. The event raised funds ... been wounded in battle and their families. Venture Construction Group is a 2016 Silver ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Research and ... Excipients Market by Type (Organic Chemical (Sugar, Petrochemical, Glycerin), ... Topical, Coating, Parenteral) - Global Forecast to 2021" ... The global pharmaceutical excipients market is projected ... CAGR of 6.1% in the forecast period 2016 to ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... "Global MEMS Devices Medical Market Analysis 2016 - Forecast to ... The report contains up to date financial ... reliable analysis. Assessment of major trends with potential impact on ... dive analysis of market segmentation which comprises of sub markets, ...
(Date:6/23/2016)... 2016 Bracket , a leading clinical trial ... clinical outcomes platform, Bracket eCOA (SM) 6.0, at the ... – 30, 2016 in Philadelphia , Pennsylvania.  ... Assessment product of its kind to fully integrate with RTSM, ... eCOA 6.0 is a flexible platform for electronic clinical outcomes ...
Breaking Medicine Technology: