Navigation Links
Treatment resistance in some cancer cells may be reversible

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
Massachusetts General Hospital

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. 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:
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... ... , ... The temporary closing of Bruton Memorial Library on June 21 due to a possible ... often overlooked aspect of head lice: the parasite’s ability to live away from a human ... but a necessary one in the event that lice have simply gotten out of control. ...
(Date:6/25/2016)... ... 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned ... the David Geffen School of Medicine at UCLA. He trained in Internal Medicine at ... fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits ... terms of the latter, setting the bar too high can result in disappointment, perhaps ... slow progress toward their goal. , Research from reveals that ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World ... with chronic pain and the benefits of holistic treatments, Serenity Recovery Center ... with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 The Academy of ... recommendations that would allow biopharmaceutical companies to ... entities that make formulary and coverage decisions, a move ... of new medicines. The recommendations address restrictions ... appear on the drug label, a prohibition that hinders ...
(Date:6/24/2016)... and SAN CLEMENTE, Calif. , June 24, ... -based mobile pulmonary function testing company, is now able to perform ... developed by ndd Medical Technologies , Inc. ... in hospital-based labs.  Thanks to ndd,s EasyOne PRO ® , ARL ... can get any needed testing done in the comfort of her ...
(Date:6/24/2016)... -- According to a new market research ... Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, 8mm, ... Purchase (Retail, Non-Retail) - Trends & Global Forecasts to ... for the forecast period of 2016 to 2021. This ... 2021 from USD 1.65 Billion in 2016, growing at ...
Breaking Medicine Technology: