Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Singapore research team identifies new drug target in deadly form of leukemia

04.06.2013
A research team led by the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has identified ways to inhibit the function of a key protein linked to stem cell-like behavior in terminal-stage chronic myeloid leukemia (CML), making it possible to develop drugs that may extend the survival of these patients.

The study, published in the prestigious international journal Proceedings of the National Academy of Sciences, is the result of a long-standing collaboration between Duke-NUS, the Experimental Therapeutics Centre at the Agency for Science, Technology and Research (A*STAR), and the Singapore General Hospital that is focused on developing effective therapies in CML.

CML is a blood cancer that has seen tremendous improvement in treatment outcomes following the introduction of tyrosine kinase inhibitor (TKI) drugs that specifically target the BCR-ABL fusion gene, a genetic abnormality that is characteristic of CML. However, when CML progresses to its terminal stage, known as the blast crisis phase, TKI drugs become ineffective and patients with blast crisis CML rapidly succumb to the disease.

"TKI therapy is highly effective in chronic phase CML, and enables most patients to survive many years. In contrast, patients with blast crisis CML usually succumb to their disease within one year, with most patients dying because they develop drug resistance to TKI therapy," said principal investigator Ong Sin Tiong, associate professor and head of the Laboratory of Hematologic Malignancies in the Cancer and Stem Cell Biology Program at Duke-NUS.

A subset of cells associated with blast crisis CML exhibit characteristics of self-renewing stem cells, suggesting that targeting this particularly malignant and drug-resistant population would be effective in treating blast crisis CML. The team therefore searched for novel targets that will specifically eliminate these cancer stem cells.

Through their efforts, the team identified a protein enzyme, known as the MNK kinase, that was abnormally activated in clinical samples taken from patients with blast crisis CML. Experiments conducted in the lab further unraveled how MNK kinase activation plays a critical role in the progression of CML to the blast crisis phase, and confers stem cell-like behavior on blast crisis cells.

The team tested a panel of drugs that inhibit MNK kinase activity and found that these MNK inhibitors were effective in preventing blast crisis cells from behaving like cancer stem cells in both in vitro laboratory tests and animal studies.

"Our studies identify the MNK kinases as an important therapeutic target in blast crisis CML, and suggest that drug inhibition of MNK kinase will be useful in overcoming TKI resistance, and improving the survival of patients with blast crisis CML," said Ong, who is also a visiting consultant at the National Cancer Center Singapore and Singapore General Hospital.

Importantly, the MNK inhibitor drugs do not appear to be toxic to normal blood stem cells, indicating that drugs targeting MNK kinases may not cause harmful side effects. Ong said he hopes the findings from this study will open new research directions in the treatment of blast crisis CML.

"We are currently collaborating with the Experimental Therapeutics Centre and Singapore General Hospital to develop new drugs to simultaneously target the MNK and the BCR-ABL kinases. The development of dual MNK and BCR-ABL kinase inhibitors to treat patients with blast crisis CML may enhance the survival of patients with this deadly disease," Ong said. He added he ho estimates it will take a few years before these drugs can enter into clinical trials for blast crisis CML.

Dr. Sharon Lim, a research fellow at Duke-NUS, is the first author of the study. Funding for the study was provided by the Duke–National University of Singapore Signature Research Program funded by A*STAR; the Ministry of Health (Singapore); and the National Research Foundation Singapore Clinician Scientist Award, awarded to Ong by the National Medical Research Council.

Juliana Chan | EurekAlert!
Further information:
http://www.dukemedicine.org

Further reports about: CML Cancer Medical Wellness Singapore blast crisis cancer stem cells stem cells

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>