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:5/31/2016)... London, Ontario (PRWEB) , ... May 31, 2016 , ... ... more than 2,000 clients already know – London is home to Ontario’s leading day ... and direction of visionary Fayez Tamba began with a unique concept to combine spa ...
(Date:5/31/2016)... ... , ... In his latest video, renowned AstroNumerologist Jesse Kalsi ... presidential candidate Donald Trump as an example, Kalsi describes the way AstroNumerology conveys ... adding numbers up,” says Kalsi. “It is about looking at each individual number, ...
(Date:5/31/2016)... , ... May 31, 2016 , ... Interest is on ... screening tool and as an orthogonal tool for RNAi hit validation. A key reason ... specific guide RNAs—allows rapid generation of CRISPR RNA (crRNA) collections in arrayed formats. ...
(Date:5/31/2016)... ... ... In a recent interview on The Greenburgh Report radio show hosted by Greenburgh, NY ... AM), leading medical insurance advocate Adria Goldman Gross discussed several eye-opening issues that have ... During the interview with Mr. Feiner that aired on May 7, 2016, Ms. Gross, ...
(Date:5/31/2016)... Chicago, IL (PRWEB) , ... May 31, 2016 ... ... industry-leading multichannel marketing services firm and statement solutions provider, for the ... released in the May 2016 issue of Advertising Age, and SourceLink ranked eighteenth ...
Breaking Medicine News(10 mins):
(Date:5/31/2016)...   Plexus Technology Group, LLC (Plexus ... systems (AIMS), is pleased to announce the addition ... of Technology. In this new capacity, Mr. Marcey ... company,s technological development. He will collaborate with each ... expansion of new products, product features and enhancements.  ...
(Date:5/31/2016)... York , May 31, 2016 ... essential ingredient in food, cosmetics and pharmaceuticals, with global ... revenues worth US$ 1.6 Bn. Demand for ... products, juices, and yogurts will continue its upward momentum ... trend will also boost positive sentiment on aloe vera, ...
(Date:5/31/2016)... Israel , May 31, 2016 ... its proprietary plant-based rhCollagen technology for tissue repair products ... Chief Scientist of Israel,s Ministry ... 12 million development project for 2016. The Chief Scientist,s grant ... year,s authorized grant, which totaled NIS 4.7 million.  ...
Breaking Medicine Technology: