Navigation Links
OHSU Cancer Institute researchers identify new approach to help control drug resistance in leukemia
Date:3/24/2008

PORTLAND, Ore. Oregon Health & Science University Cancer Institute researchers have found that an experimental drug known as SGX393 is effective against Gleevec-resistant chronic myeloid leukemia (CML). The results of their study will be published the week of March 24th in the Proceedings of the National Academy of Sciences.

Gleevec, the targeted therapy identified by OHSU Cancer Institute Director Brian Druker, M.D., is the current first line therapy for CML. Gleevec works by inhibiting the activity of Bcr-Abl, an enzyme that is present only in CML cells and upon which these cells depend for survival. Although most patients with CML respond dramatically to Gleevec, some patients develop resistance to the drug. Most Gleevec-resistant CML cells carry a mutated form of Bcr-Abl, which prevents Gleevec from functioning properly. The second-generation drugs Sprycel and Tasigna have been developed as largely successful treatments for Gleevec-resistant patients. However, one mutated form of Bcr-Abl, called T315I, is resistant to all three clinical CML drugs and is a frequent cause of relapse.

Michael Deininger, M.D., Ph.D., head of the Hematologic Malignancies Section, and his research team in the OHSU Cancer Institute have shown that SGX393, developed by SGX Pharmaceuticals, Inc., San Diego, Calif., inhibits the T315I mutant and most, but not all, other Gleevec-resistant mutants. This was shown to be true using laboratory models as well as leukemia cells from patients with CML.

Researchers then took this success a step further. Using a method developed in their laboratory to rapidly and accurately forecast drug-resistant Bcr-Abl mutations, Deininger and colleagues established a resistance profile for SGX393. Though SGX393 showed a handful of mutation weak spots, the T315I mutation was absent among thousands of samples surveyed in the laboratory. In contrast, T315I was frequently recovered when running the screen with any of the other drugs.

Because the resistance profile of SGX393 nicely complemented those of the other drugs and none of the drugs individually controlled all of the mutations, we extended our study to look at using a combination of the drugs. Remarkably, we found that the combination of SGX393 with either Sprycel or Tasigna completely suppressed resistance, said Christopher Eide, research technician. He is a co-author with fellow OHSU Cancer Institute researchers Thomas OHare, Ph.D., Jeffrey Tyner, Ph.D., Amie Corbin, and Matthew Wong.

Our pre-clinical study suggests that rationally combining two Bcr-Abl inhibitors with different resistance profiles could provide a dragnet to protect against resistance, OHare said. The idea is that each drug is especially adept at handling certain Bcr-Abl mutants and that the drugs can team up to eliminate cells carrying mutants that neither drug could eliminate on its own.

The effectiveness and safety of Gleevec for most patients remains remarkable, said Deininger. However, it is important for patients to know that, with the addition of a drug such as SGX393 to the set of current approved CML drugs, we may have the therapeutic tools to achieve and maintain even more effective and longer control of their cancer. This is not equivalent to a cure, but it could potentially represent an important advance in the management of CML.


'/>"/>

Contact: Christine Decker
deckerch@ohsu.edu
503-494-8231
Oregon Health & Science University
Source:Eurekalert

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. Survival differences by race most apparent in advanced stages of breast cancer
3. MRI finds breast cancer before it becomes dangerous
4. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
5. Pathway links inflammation, angiogenesis and breast cancer
6. Radiologists encouraged to look beyond cancer for clinically unseen diseases
7. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
8. Immune deficiency linked to a type of eye cancer
9. Drop in breast cancer incidence linked to hormone use, not mammograms
10. Breast cancer prevention practices vary across Canada
11. First biomarker discovered that predicts prostate cancer outcome
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2017)... Silver Spring, MD (PRWEB) , ... January 18, 2017 , ... ... and financial consultations to families and business owners in central Maryland and the DC ... community. , Heart disease kills 787,000 people nationally every year, making it the #1 ...
(Date:1/18/2017)... N.J. (PRWEB) , ... January 18, 2017 , ... ... delivery technologies and development solutions for drugs, biologics and consumer health products, today ... will be presenting at the upcoming WCBP Conference, to be held at the ...
(Date:1/18/2017)... Hills, CA (PRWEB) , ... January 18, 2017 ... ... of dental problems ranging from gum disease to enamel erosion, and those dental ... the Massachusetts Department of Public Health, many pregnant women are failing to get ...
(Date:1/17/2017)... ... January 17, 2017 , ... Gym Source, America’s leading retailer of ... at South Dixie Hwy in Miami, FL. , “We are elated to be opening ... innovative in-store concept is designed to give clients a seamless and motivating shopping experience.” ...
(Date:1/17/2017)... Phoenix, AZ (PRWEB) , ... January 17, 2017 ... ... new and improved supplement, Healthful-Flex. , The company, owned and operated by ... the public at a reasonable price with the highest level of customer service. ...
Breaking Medicine News(10 mins):
(Date:1/18/2017)... After the recent election cycle, it is clear ... for medical and recreational purposes are shifting. The evidence shows ... of cannabis, but the focus is coming from both the ... North American legal cannabis market posted $6.7 billion in revenue ... projects sales will grow at a compound annual growth rate ...
(Date:1/17/2017)... , Jan. 17, 2017 Precision medicine ... for the treatment of disease. The approach allows ... to a therapy. The approach studies the individual ... lifestyle and environment. In January 2015, Precision Medicine ... to all diseases with more than one million ...
(Date:1/17/2017)... , Jan. 17, 2017 EU5 Glucose Monitoring ... new report, "EU5 Glucose Monitoring Market Outlook to 2022", ... market. The report provides value, in millions of US ... market segments - Blood Glucose Meters, Blood Glucose Test ... shares and distribution shares data for each of these ...
Breaking Medicine Technology: