Navigation Links
OHSU Cancer Institute researchers identify new approach to help control drug resistance in leukemia

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
Oregon Health & Science University

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:
(Date:6/27/2016)... ... June 27, 2016 , ... ... strategic partnership with Connance, a healthcare industry leader providing predictive analytics to ... technology combine to provide health systems, hospitals and ambulatory surgical centers with ...
(Date:6/26/2016)... (PRWEB) , ... June 27, 2016 , ... Quality metrics ... yet in many ways they remain in the eye of the beholder, according to ... a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... Cary, North Carolina (PRWEB) , ... June 26, 2016 , ... ... the release of a new product that was developed to enhance the health of ... harvested for centuries. , The two main herbs in the PawPaws Cat Kidney ...
(Date:6/25/2016)... ... 2016 , ... Experts from the American Institutes for Research ... June 26-28, 2016, at the Hynes Convention Center in Boston. , AIR experts ... planning, healthcare costs and patient and family engagement. , AIR researchers will be ...
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX users ... - CEO of Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 ... Pro X . Simply select a ProHand generator and drag it above media or ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on the ... announced that patient enrollment in its ongoing randomized ... has exceeded 50% of its 24-patient target. Capricor ... the third quarter of 2016, and to report ...
(Date:6/23/2016)...  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new affiliate with operations headquartered in ... . ... ... ... Astellas ...
(Date:6/23/2016)... Tenn. , June 23, 2016 /PRNewswire/ ... automating, integrating and transforming the patient payment ... of several innovative new products and services ... of its revenue cycle offerings. These award-winning ... more efficient workflows, remain compliant in an ...
Breaking Medicine Technology: