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:3/29/2017)... ... March 29, 2017 , ... Full Contact K9, an ... Pet Protect Law that assists dog owners in creating legally-enforceable pet trusts ... in taking the natural next step to protect their new companion. Says Evan Dunbar, ...
(Date:3/29/2017)... ... ... Brand EXOUS Bodygear announced today a special sale price for the EX-701 Knee ... the price will be only $19.97. The EXOUS Bodygear 65cm exercise ball ... $19.97). , The special promotional prices are to help individuals get their products at ...
(Date:3/29/2017)... Carnegie, OK (PRWEB) , ... March 29, 2017 ... ... can now receive FASTBRACES® in Carnegie, OK, from Dr. Jamie Cameron, ... to straighten teeth efficiently, compared to traditional orthodontic treatment. Depending on each patient’s ...
(Date:3/29/2017)... MD (PRWEB) , ... March 29, 2017 , ... ... is proud to announce the finalization of the company’s executive management team with prominent ... and leading operations is Curio Wellness’ Chief Operating Officer, Ted Dumbauld , who ...
(Date:3/29/2017)... North Hollywood, CA (PRWEB) , ... March 29, 2017 , ... ... and Northridge , is now offering laser dental treatments. Dental lasers are safe ... treatments. Laser dentistry expands patients’ options and can improve the overall quality of care. ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... HUNTINGTON BEACH, Calif. , March 29, 2017 ... treatment have recognized remote monitoring devices like  Soberlink ... monitoring.   The consensus paper, published in early ... "feasible, practical and valuable in managing patient recovery." ... published in the Journal of Addiction Medicine, detail ...
(Date:3/29/2017)... leader in accelerated orthodontics, OrthoAccel ® Technologies, Inc. ... Manal Ibrahim , Kenji Ojima , Ivan ... microlecture presenters at the AcceleDent ® booth (#3037) ... Session, April 21-25, 2017. Orthodontists and their staff are ... a.m. On the opening morning of AAO exhibitions, Sat., ...
(Date:3/29/2017)... N.J. , March 29, 2017  Glenmark ... results for GSP 301, an investigational fixed-dose combination ... (665 mcg) administered twice-daily as a nasal spray ... rhinitis. These results are from a recently completed ... of GSP 301 combination therapy versus mometasone, olopatadine ...
Breaking Medicine Technology: