Navigation Links
New Test Predicts CLL’s Sensitivity to Experimental Drug

Dana-Farber Cancer Institute scientists have developed a test that is first to identify - which malignant blood cells are highly vulnerable to a promising// type of experimental drugs that unleash pent-up "cell suicide" factors to destroy the cancer.

The researchers demonstrated that chronic lymphocytic leukemia, CLL, which is diagnosed in 10,000 Americans each year, is an easy mark for the new drug because the cancerous cells are strongly dependent on a particular survival molecule, Bcl-2, that keeps the self-destruct signals at bay. They showed that the investigational drug neutralizes the Bcl-2 action, unleashing molecules that trigger suicide in the cancer cells, a process known as programmed cell death or apoptosis.

The research in the laboratory of Anthony Letai, MD, PhD, of Dana-Farber, is described in the January issue of The Journal of Clinical Investigation. The lead author is Victoria Del Gaizo Moore, PhD, a member of the Letai group.

Letai was a colleague of the late Stanley J. Korsmeyer, MD, of Dana-Farber, who discovered the key role in cancer played by anti-apoptosis molecules such as Bcl-2, which promote the survival of cells that are damaged or abnormal despite the body's efforts to eliminate them through apoptosis.

Inspired by this pioneering research, drug companies have begun testing novel Bcl-2 inhibiting drugs designed to restart the natural death processes thwarted by the survival molecule.

Letai said that his group has tested Abbott's investigational compound ABT-737 against cultured CLL cells with striking results. "We've treated CLL samples from several dozen patients, and each has responded to a very low concentration of the drug," said Letai. "We find it particularly interesting that the cells died within four hours."

Cells from CLL, a currently incurable disease, are vulnerable to this dramatic reversal of fortune because they are "primed for death;" they are survivi ng only because Bcl-2 proteins are blocking powerful cell-death molecular signals by holding them hostage. Primed cells, Letai explained, are like a car with a revved-up engine on the edge of a cliff, restrained only by its emergency brake; if the brake was released, the car would plunge over the cliff.

Drugs such as ABT-737, in effect, release the brake. The drug molecules liberate the pro-death signaling molecules from their Bcl-2 captors. These pro-apoptosis molecules -- a key one is called BIM -- then trigger a chain of events that cause the cell's power plants, or mitochondria, to rupture and spill out chemicals that cause the cell to die and be tagged for disposal. This class of drugs is expected to be relatively non-toxic to most normal cells, which are much less dependent on Bcl-2 function than are cancer cells to stay alive.

"It's essential to figure out which cancers are going to respond to the drug by identifying the cells that are dependent on Bcl-2 for survival," said Letai, who is also an assistant professor of medicine at Harvard Medical School. "Up to now there hasn't been a way to do this."

In developing the test, the Letai team first isolated mitochondria from cancer cells; then they exposed them to protein fragments – peptides – that were known to interact with survival molecules like Bcl-2. "If they interact, then the cell is primed to die, and the test will identify which of the survival molecules is keeping the cells alive," he added. "Then you know that to kill the cell, you have to target Bcl-2."

The researchers have dubbed the test "BH3 profiling" because the array of protein fragments is known as "BH3 domains." Letai said work is under way to make the laboratory profiling operation more automated, looking toward a time when it could be used on a routine basis to assess the vulnerability of patients' cancers to compounds that antagonize BCL-2 or related anti-death proteins.

"This is a totally new class of drugs and has the potential to be a major addition to how we treat cancer," he said.

Source-Eurekalert
SR
'"/>




Related medicine news :

1. Restricted Activity Predicts Disability
2. Fitness Level Predicts Stroke
3. PSA Can Predicts The Treatment Response In Advanced Prostate Cancer
4. Being Teased Predicts Poor Psychological Functioning in Youth With Cleft Lip
5. Model Predicts Colon Cancer Inheritable Genetic Defects
6. Formula Predicts Osteoporotic Fracture Risk
7. Computer Tool Predicts Effectiveness Of Microbicides
8. New Genetic Test Predicts Eye-Cancer Patients Futures
9. Technology Predicts Outcome of Child Heart Surgery
10. A Secret Dossier Predicts Major Changes At NHS, England
11. Activation of a Particular Brain Region Predicts Altruism: Study
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:10/13/2017)... ... October 13, 2017 , ... Southern ... and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice Frueh, ... cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU School ...
(Date:10/13/2017)... ... ... Apple Rehab Shelton Lakes , which specializes in the delivery of sub-acute ... of a disaster drill on October 3rd. , Apple Rehab participated with the Shelton ... well as the Connecticut Long Term Care Mutual Aid Plan (LTC-MAP). The LTC-MAP ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... The Visiting ... Day Market. Featuring a collection of specialty vendors and unique items from across the ... and quality-focused health and wellness services offered by the VNA. The boutique will ...
(Date:10/13/2017)... Milford, NJ (PRWEB) , ... October 13, 2017 , ... ... weekend at scenic Alexandria Park in Milford, NJ. This free event, sponsored by ... and physical activity. The fun run is geared towards children of all ages; ...
(Date:10/13/2017)... ... 2017 , ... Talented host, actor Rob Lowe, is introducing ... new episode of "Success Files," which is an award-winning educational program broadcasted on ... subject in-depth with passion and integrity. , Sciatica occurs when the sciatic nerve ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... , Oct. 4, 2017  South Korean-based healthcare product ... training aide "cprCUBE" on Kickstarter. The device will educate ... cardiac arrests with better efficiency compared to the dated ... real-time feedback on efficacy of the compression for a ... has a goal to raise $5,000. ...
(Date:10/2/2017)... Diplomat Pharmacy, Inc. (NYSE: DPLO ... LLC , and named its founder as Diplomat,s chief ... Tennessee , will operate under Diplomat subsidiary ... offerings for health care partners to include IT outsourcing, ... "In an interoperable world, technology delivers comprehensive insight ...
(Date:10/2/2017)... announces the European launch of their new low volume, high throughput ... Cambridge, U.K on October 4th. The new ... unprecedented speed and sensitivity while using far less sample volume through ... ... ...
Breaking Medicine Technology: