Navigation Links
Treatment resistance in some cancer cells may be reversible
Date:4/1/2010

The ability of cancer cells to resist treatment with either targeted drug therapies or traditional chemotherapy may, in some cases, result from a transient state of reversible drug "tolerance." In a paper that will appear in the journal Cell and is receiving early online release, researchers from the Massachusetts General Hospital (MGH) Cancer Center report finding small populations of drug-tolerant cells from several different types of tumors and identifying aspects of the underlying mechanism.

"While resistance to cancer drugs can result from rare, pre-existing genetic mutations that emerge in response to treatment, accumulating evidence has pointed to additional nongenetic, potentially reversible mechanisms," says Jeffrey Settleman, PhD, of the MGH Cancer Center, who led the study. "In cell lines derived from several different types of cancer we found subpopulations of cells that display a transient ability to tolerate exposure to toxic drugs, which was associated with structural changes in the cells' DNA and points to a therapeutic strategy that could potentially prevent resistance from developing."

When cells within a tumor that had responded to treatment resume uncontrolled growth, drug therapy is usually stopped. But there have been many reports indicating that some tumors can regain sensitivity to the previously ineffective treatment after a "drug holiday." In order to investigate the mechanism underlying that phenomenon, the researchers tested several tumor-derived cell lines against drugs to which the original tumors were known to be sensitive.

In each of the lines they examined, a small number of tumor cells survived exposure to concentrations of drug 100 times greater than levels that killed the vast majority of the cells. But when these drug-tolerant cells were placed in an environment without the drug, their offspring eventually regained sensitivity to the drug.

Further investigation revealed that drug tolerance was associated with changes in gene expression, implicating alterations in chromatin, the chromosome structure consisting of DNA wrapped around a protein scaffolding. The researchers found that a particular chromatin-modifying enzyme was required for the development of tolerance, and while no currently available drug inhibits that protein, agents that block an associated group of enzymes did cause the death of drug-tolerant but not drug-sensitive cells.

"We believe this kind of reversible drug resistance may be a fundamental property of many tumor cell populations," says Settleman. "Determining whether what we see in cell cultures will translate into what happens in patients is essential, and we've already started a clinical trial to see if combining a chromatin-modifying agent with the targeted lung-cancer drug erlotinib [Tarceva] may prevent or delay the development of resistance. We're also using our cell culture models to further explore the underlying mechanisms." Settleman is the Laurel Schwartz Professor of Medicine at Harvard Medical School.


'/>"/>

Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Steroids May Be Overrated in Treatment of COPD
2. Experimental stem cell treatment arrests acute lung injury in mice, study shows
3. Entest BioMedical Enters into LOI with Advanced Light Devices to Develop Laser Platform for Stem Cell / Laser COPD Treatment
4. New study shows effectiveness of MEND program in prevention and treatment of pediatric obesity
5. New York City Surgeon Develops All-Natural Treatment for Wrinkles and Scars
6. Novelty lures rats from cocaine-paired settings, hinting at new treatments for recovering addicts
7. Northeast Chiropractic, PC Revolutionizes Pain Management Without Medication, Now Offering New and Unique Blend of Treatments
8. Autism-Supplements.com and Generation Rescue Work Together to Raise Money for Biomedical Autism Treatments
9. Biomarker could help doctors tailor treatment for rheumatoid arthritis
10. St. John Health System Brighton Hospital Signs Letter of Intent to Assist Saudi Arabia in Developing New Addiction Treatment Hospital in Riyadh
11. Jefferson neurosurgeon helps draft new treatment guidelines for brain metastases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/22/2017)... , ... September 22, 2017 , ... Happy Living’s mission ... time - carries it into the entertaining and delicious worlds of theatre and ... (founder of Happy Living) convinced him to turn his play into a book. The ...
(Date:9/22/2017)... ... 22, 2017 , ... TopConsumerReviews.com recently awarded their highest five-star ... promote pancreatic health and regulate blood sugar levels . , Preventing diabetes ... negative side effects, and with the changes in today’s healthcare industry, not everyone ...
(Date:9/22/2017)... ... 22, 2017 , ... Silicon Valley startup Enke Life has ... Their electric toothbrushes aggressively attack oral bacteria by reducing dental plaque and other ... edge Enke technology with a premium timeless design, they want to redefine the ...
(Date:9/22/2017)... ... September 22, 2017 , ... The freshly released ... doorstep. According to Smart Mart, customers can now order vegetable, fruit, snacks, dairy, ... customers can find clothing at discounted prices. Apart from this, Smart Mart has ...
(Date:9/21/2017)... Viejo, CA (PRWEB) , ... September 21, 2017 , ... ... been so fun and easy to do. Users can select from up to two ... all with a click of a mouse all within Final Cut Pro X. ...
Breaking Medicine News(10 mins):
(Date:9/19/2017)... HistoSonics, Inc., a venture-backed medical device company developing a non-invasive, robotically assisted, platform ... leadership team developments today:   ... ... Tom Tefft ... Veteran medical device executive Josh Stopek , PhD, who has led ...
(Date:9/12/2017)... and NEW YORK , Sept. 12, 2017 ... performance ratings for global supply chains, has published the first annual edition ... CSR performance of more than 20,400 companies evaluated by EcoVadis, based on ... 2015 and 2016. ... EcoVadis Global CSR Risk & Performance Index ...
(Date:9/9/2017)... , Sept. 9, 2017  Eli Lilly and ... primary and secondary endpoint data for lasmiditan, an investigational, ... which demonstrated statistically significant improvements compared to placebo in ... highlighted today at the 18th Congress of the International ... "The data presented today demonstrate lasmiditan,s potential ...
Breaking Medicine Technology: