Navigation Links
Combination of 2 novel anti-cancer agents may help fight CML resistant to current therapy
Date:5/29/2008

Virginia Commonwealth University Massey Cancer Center researchers have identified that a combination of novel anti-cancer compounds is able to kill chronic myelogenous leukemia cells previously resistant to conventional forms of therapy.

Chronic myelogenous leukemia, or CML, is a cancer of the bone marrow caused by a specific genetic abnormality and is one of the more common forms of leukemia. Imatinib mesylate, or Gleevec, is a highly effective anti-cancer agent that has revolutionized the course of therapy for patients with CML. It works by inhibiting the activity of a mutant protein, known as Bcr/Abl, which is responsible for the disease. However, despite initial success, patients eventually become resistant to imatinib mesylate, often through the development of further mutations in the Bcr/Abl protein.

According to Steven Grant, M.D., Masseys associate director for translational research and co-leader of the cancer centers cancer cell biology program, and senior author of the study, resistance to imatinib mesylate prompted the search for newer agents that are active against the mutated forms of Bcr/Abl. Such agents include MK-0457, a Bcr/Abl kinase inhibitor that also targets another protein called an aurora kinase. Aurora kinase plays an important role in mitosis and cell division. In preclinical studies, MK-0457 is active against the T315I Bcr/Abl mutation, a major cause of imatinib resistance, and has shown promise in early clinical trials, Grant said.

In this study, Grant and colleagues examined the effects of combining MK-0457 with vorinostat, a novel targeted agent that has recently been approved for the treatment of cutaneous T-cell lymphoma. They found that this combination leads to a dramatic induction of apoptosis, or programmed cell death in CML cells, including imatinib-resistant cells bearing the T315I or other mutations. The article was pre-published as a First Edition Paper in Blood, the journal of the American Society of Hematology, which appeared online May 27.

Further, Grant said that the interaction between these agents may occur at multiple levels, including potentiation of Bcr/Abl inhibition as well as enhanced disruption of aurora kinase and mitosis. In addition, the group demonstrated that vorinostat-mediated up-regulation of Bim, a pro-apoptotic protein, contributed significantly to the effectiveness of this regimen.

Our findings suggest it may be possible to develop a clinical regimen combining a third-generation Bcr/Abl kinase and aurora kinase inhibitor, such as MK-0457, with histone deacetylase inhibitors, such as vorinostat, Grant said.

Theoretically, this combination could improve upon the results of Bcr/Abl kinase inhibitors administered alone, particularly in the case of imatinib-resistant disease, he said. Further preclinical studies are underway to test this hypothesis.


'/>"/>

Contact: Sathy Achia Abraham
sbachia@vcu.edu
804-827-0890
Virginia Commonwealth University
Source:Eurekalert

Related medicine news :

1. Promising drug combination may help those with ocular melanoma that has spread
2. Combination therapy reverses effects of portal hypertension in rats
3. Combination vaccines okay for infants, study shows
4. Antidepressants and painkillers - a dangerous combination
5. Intra-arterial combination chemotherapy induces long-term survival for hepatocellular carcinoma
6. U.S. Oncology Initiates Complete Phase Ib Trial of Brostallicin Combination Therapy in Advanced Solid Tumors
7. Drug combination might offer hope for patients deadly brain tumors
8. EpiCept to Present Preclinical Studies of EPC2407 in Combination With Anti-Angiogenic and Chemotherpeutic Agents at the AACR-NCI-EORTC International Conference
9. Combination targets: some drugs may work best when they work together
10. MAP Pharmaceuticals Initiates Phase 2a Clinical Trial of Combination Therapy in Adult Patients with Asthma
11. Quality Control: Nissan Quest to Feature micronAir(R) Combination Cabin Air Filters
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/26/2017)... ... 26, 2017 , ... Six greater Bay Area roller derby leagues are partnering with Brown Paper ... widely attended series of blood drives in California, beginning July 29. Make ‘Em Bleed roller ... years -- enough to have helped to save up to 2700 lives. , “The Make ...
(Date:7/26/2017)... (PRWEB) , ... July 26, 2017 , ... A major ... processes. Inconsistent results freeze drying samples and a lengthy freeze dry cycle are a ... will discuss freeze drying techniques, as well as new accessories and advancements in laboratory ...
(Date:7/26/2017)... ... July 26, 2017 , ... “We are dentists and we thought there ... Jose, Calif., “so we invented the MAGNETIC/ LOCK BRACKETS.” , The patent-pending MAGNETIC/ LOCK ... In doing so, it offers an effective alternative to traditional braces. As a result, ...
(Date:7/26/2017)... ... ... to sign up for the new One-A-Month Essential Oil Club for fun and wellness. ... and author of numerous books on essential oils. , , Members ... Two items are included in the December mailing. , A HOW ...
(Date:7/26/2017)... ATLANTA, Ga. (PRWEB) , ... July 26, 2017 , ... ... and equal access to medicine for everyone affected by diabetes, is excited to announce ... of its Global Ambassador Program. , Established in 2005, the Team Type 1 ...
Breaking Medicine News(10 mins):
(Date:7/14/2017)... , July 14, 2017 Endo International plc (NASDAQ: ... on Tuesday, August 8, 2017.  Members of its senior management team ... markets open at 8:30 a.m. ET. The dial-in ... (866) 497-0462, International (678) 509-7598, and the passcode is 45397076. Please ... A replay of the call ...
(Date:7/12/2017)... , July 12, 2017 CarpalAID is a revolutionary ... braces or surgery. Carpal tunnel syndrome affects more than ... at twice the rate of men. The common methods of treating ... mobilization with uncomfortable hand braces or gloves. ... CarpalAID is a clear patch ...
(Date:7/11/2017)... , July 11, 2017  Sysmex America, Inc., ... diagnostic testing equipment as well as middleware information ... way to make quality assurance easier and more ... is well known for the innovation that it ... Monitor elevates quality assurance processes to a new ...
Breaking Medicine Technology: