Cancer cell line developed that is resistant to new cancer therapy

A cancer cell line that is resistant to one of the newest classes of cancer treatments has been developed by researchers who already are using it to determine what else to give patients when this happens.

“The ultimate goal is to be able to understand how cancer cells develop resistance and to have forward-thinking strategies about how to combat that resistance,” says Dr. Warren Fiskus, postdoctoral fellow in the laboratory of Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center.

Resistant cells emerged by treating human leukemic cells with regular, increasing doses of histone deacetylase, or HDAC, inhibitors, similar to what patients would receive. “At each dose level, there were some cells that did die,” says Dr. Fiskus. “Ultimately, we isolated a population of cells that were resistant to very high concentrations of these agents and other agents in the same class.”

Dr. Fiskus is presenting the findings Dec. 11 during the American Society of Hematology’s 49th Annual Meeting and Exposition in Atlanta.

They found the HDAC inhibitor-resistant cell line resistant to many therapies, including more standard treatment such as chemotherapy, but highly sensitive to heat shock protein 90, or hsp90, inhibitors, another emerging cancer treatment.

“As part of their resistance mechanisms, they acquired greater sensitivity to hsp90 inhibitors,” says Dr. Bhalla, Cecil F. Whitaker Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer. “This creates a potential combination that can be tested in mouse models and ultimately clinical trials.”

HDAC and hsp90 inhibitors are both being studied in combination with other cancer therapies but not each other. However the MCG researchers, who already have published work indicating a synergistic effect, were not surprised by what they found.

“Resistance to HDAC inhibitors is going to emerge, so you need a cellular model to understand mechanisms of resistance and an in vivo model, a mouse model typically, to test new combinations you design based on studies in culture,” says Dr. Bhalla.

The researchers have put the cell line into a mouse model and other scientists already are asking for the resistant cell line, he says.

“This particular cell line can be used to really look at newer agents and new combinations in vitro and in vivo and see if they are safe and effective together,” Dr. Fiskus says.

Heat shock proteins are protein caretakers, activating genes that ultimately make proteins, move them around cells and fold them into shape for proper function. Misfolded proteins can cause cancer.

MCG is participating in an early-phase clinical trial of the oral HDAC inhibitor, LBH589, developed by Novartis Corp. Studies also are underway for some innovative uses of hsp90 inhibitors, including Dr. John Catravas’ studies of its potential as an anti-angiogenesis agent and Dr. Abdullah Kutlar’s studies to see if it can reduce morbidity and related lung problems in sickle cell disease by suppressing inflammation.

Source: Medical College of Georgia

Related stories:

Parsing the genome of a deadly brain tumor
The most comprehensive to-date genomic analysis of a cancer – the deadly brain tumor glioblastoma multiforme – shows previously unrecognized changes in genes and provides an overall view of the missteps in the pathways that govern the growth and behavior of cells, said members of The Cancer Genome Atlas Research Network in a report that appears online today in the journal Nature.
Atomic structure of the mammalian 'fatty acid factory' determined
Mammalian fatty acid synthase is one of the most complex molecular synthetic machines in human cells. It is also a promising target for the development of anti-cancer and anti-obesity drugs and the treatment of metabolic disorders. Now researchers at ETH Zurich have determined the atomic structure of a mammalian fatty acid synthase. Their results have just been published in Science magazine.
Studies spot numerous undiscovered gene alterations in pancreatic and brain cancers
HHMI investigators have detected a multitude of broken, missing, and overactive genes in pancreatic and brain tumors, in the most detailed genetic survey yet of any human tumor. Some of these genetic changes were previously unknown and could provide new leads for improved diagnosis and therapy for these devastating cancers.
You can be replaced: Immune cells compensate for defective DNA repair factor
A new mouse model has provided some surprising insight into XLF, a molecule that helps to repair lethal DNA damage. The research, published by Cell Press in the September 5th issue of the journal Molecular Cell, suggests that although XLF shares many properties with well known DNA repair factors, certain cells of the immune system possess an unexpected compensatory mechanism that that can take over for nonfunctional XLF.
Unsuccessful drug against anxiety opens a novel gateway for the treatment of cancer
Unsatisfying drug for anxiety reveals scientists a promising novel anti-cancer drug target. Cancer cells have multiple ways to avoid apoptosis, programmed cell death the means by which organisms deal with defective cells. One defense is to produce quantities of phosphatic acid, a phospholipid constituent of cellular membranes.
Stem cell research puts interstate rivalry on hold
Victoria and New South Wales have put aside their competitive interstate rivalry to collaborate on a stem cell research project, as announced by Innovation Minister Gavin Jennings and NSW Minister for Science and Medical Research, Verity Firth, today.
NC State first university in nation to offer canine bone marrow transplants
Dogs suffering from lymphoma will be able to receive the same type of medical treatment as their human counterparts, as North Carolina State University becomes the first university in the nation to offer canine bone marrow transplants in a clinical setting.
New nano device detects immune system cell signaling
Scientists have detected previously unnoticed chemical signals that individual cells in the immune system use to communicate with each other over short distances.

News discussion:

Medicine & Health news