Navigation Links
'Reprogrammed' treatment-resistant lymphomas respond to cancer drugs
Date:8/16/2013

PHILADELPHIA A phase I clinical trial showed diffuse, large B-cell lymphomas (DLBCLs) resistant to chemotherapy can be reprogrammed to respond to treatment using the drug azacitidine, according to a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

Patients whose lymphomas recur after initial chemotherapy are treated with a combination of approaches, including high-dose chemotherapy followed by a stem cell transplant. However, some patients have tumors that do not respond to these extensive second treatments, and many of these patients die within two years of diagnosis.

"When lymphomas are formed, they shut down the cellular programs that sense that something is wrong in the cells. Once these fail-safe mechanisms that trigger cell death are shut down, it becomes difficult to kill the tumor with chemotherapy," said Leandro Cerchietti, M.D., assistant professor at the Hematology and Oncology Division of Weill Cornell Medical College in New York. "Our study showed that using low concentrations of the DNA methyltransferase inhibitors decitabine or azacitidine, these fail-safe mechanisms can slowly be awakened to induce lymphoma cell death when chemotherapy is administered."

Cerchietti and colleagues conducted a phase I trial in patients with newly diagnosed DLBCL. Eleven of the 12 patients enrolled were more than 60 years old when diagnosed, which meant that they were at high risk for tumor recurrence after initial treatment. The patients were treated with azacitidine, in escalating doses, eight days prior to initiation of six cycles of standard chemotherapy. Side effects from pretreatment with azacitidine were minimal. Two patients who were treated with the maximum dose of azacitidine had dose-limiting toxicities.

Of the 12 patients, 11 had a complete response and 10 remained in complete remission for up to 28 months.

"We showed that aggressive lymphomas can be reprogramed to a more benign disease," said Cerchietti. "We think this work has the potential to change the standard of care for patients with aggressive lymphomas."

The researchers conducted the clinical trial based on the results of their extensive preclinical experiments to determine the mechanisms by which lymphomas evade chemotherapy drugs. They found that compared with normal cells, all DLBCLs possess a high degree of aberrant DNA methylation, a process which "silences" certain genes, causing resistance to treatment.

Using DLBCL cells and mice bearing human lymphoma xenografts, the researchers showed that DNA methyltransferase inhibitors are most effective if administered prior to chemotherapy, but not concurrently. They also found the gene SMAD1 to be silenced in the unresponsive tumors.

When the researchers looked for SMAD1 status in the biopsy specimens collected from patients enrolled in the phase I trial, they found that after treatment with azacitidine, there was a decrease in SMAD1 methylation and increase in SMAD1 protein, providing proof of principle.

Cerchietti and colleagues are currently conducting clinical trials with patients with lymphomas whose tumors failed to respond to standard therapies. They are in the process of conducting larger, multicenter trials to extend this treatment to other cancers as well.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Protein lost in tumors blocks normal cells from being reprogrammed into stem cells
2. Some patients with treatment-resistant colorectal cancers may have a new option
3. A new route for tackling treatment-resistant prostate cancer
4. High-dose Vorinostat effective at treating relapsed lymphomas
5. High Complexity Laboratory Testing Supports New Targeted Therapies for Leukemias and Lymphomas
6. Mayo Clinic completes first genome-wide analysis of peripheral T-cell lymphomas
7. Transvaginal Mesh Lawsuit News: Rottenstein Law Group LLP Responds to $250,000 Bard Mesh Trial Verdict
8. National Law Firm Baron and Budd Responds to Disproportionate Harm Brought to Women Using Lipitor, According to Study
9. Human cells respond in healthy, unhealthy ways to different kinds of happiness
10. Ecommerce Solution Expert Shopping Cart Elite Adds Dynamic Tags for Populating the Auto-Responder Support Desk Messages
11. New Statistics Indicate Increase in Mental Health Issues Among Children, UBH Denton Responds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/7/2016)... ... December 07, 2016 , ... ODU, a worldwide ... US market its advanced highly customizable contact technology solutions. , ODU Single Contact ... technologies are ideal for a wide range of applications that require customization from ...
(Date:12/7/2016)... ... December 07, 2016 , ... Baciocco Brothers Insurance Agency, ... in the Sacramento/Folsom region, is initiating a charity event to raise support and ... Another Chance treatment center in Sacramento works to provide area teens and families ...
(Date:12/7/2016)... ... December 07, 2016 , ... One of two inventors from ... securement tape is painful for her. "This is why the co-inventor and I have ... said. , They then created a prototype of the patent-pending AV-AIR, a device that ...
(Date:12/7/2016)... (PRWEB) , ... December 07, 2016 , ... A. Kevin ... owners and families throughout the Five Boroughs, is launching a charity drive to raise ... to continue the traditions and spirit of marines and Navy FMF Corpsmen. Working closely ...
(Date:12/7/2016)... ... 2016 , ... Sharon Kleyne, host of the nationally syndicated radio program, The ... of America, declared on her radio program in November 2016 the need to educate ... bullies attack leaders in corporate America, they are trying to take advantage of successful ...
Breaking Medicine News(10 mins):
(Date:12/6/2016)... , Dec. 6, 2016 Eurofins ... accreditation from the College of American Pathologists (CAP) ... (CLIA) for its new laboratory in ... moved its North American headquarters. "Our ... sequencing -- which is still considered the ,Gold ...
(Date:12/6/2016)... , Dec. 6, 2016 Two new disaster ... in a simulated mass casualty event Tuesday at John ... The technology debuted before an audience including ... representatives from Homeland Security, Federal Law Enforcement Agencies, and ... known as HiRO (Health Integrated Rescue Operations), was developed ...
(Date:12/6/2016)... , Dec. 6, 2016  Arcturus Therapeutics, Inc. ... company, announced today that it entered into collaboration ... therapeutics for the treatment of NASH and other ... delivery platform LUNARâ„¢ and UNA Oligomer chemistry. The ... Takeda,s long-standing commitment to and expertise in GI ...
Breaking Medicine Technology: