Navigation Links
Cisplatin-resistant cancer cells sensitive to experimental anticancer drugs, PARP inhibitors
Date:4/2/2013

PHILADELPHIA Poly (ADP-ribose) polymerase inhibitors may be a novel treatment strategy for patients with cancer that has become resistant to the commonly used chemotherapy drug cisplatin, according to data from a preclinical study published in Cancer Research, a journal of the American Association for Cancer Research.

"Cisplatin is one of the most widely used conventional, anticancer chemotherapy drugs," said Guido Kroemer, M.D., Ph.D., professor at University Paris Descartes in Paris, France. "Unfortunately, most patients respond only transiently to cisplatin therapy because their cancer cells develop ways to resist the effects of the drug."

Kroemer and colleagues set out to identify the biochemical changes that arise as cancer cells become resistant to cisplatin in the hope that the information could provide clues to potential new therapies. They focused their study on non-small cell lung cancer (NSCLC) cells because NSCLC is the leading cause of cancer-related morbidity and mortality worldwide and patients with NSCLC are frequently treated with cisplatin, according to Kroemer.

The researchers found that most NSCLC cell lines resistant to cisplatin had high levels of the protein poly (ADP-ribose) polymerase 1 (PARP1) and elevated amounts of poly (ADP-ribosyl) (PAR). In addition, they found that the PARP1 was hyperactivated. They observed similar results for cisplatin-resistant mesothelioma, ovarian cancer and cervical cancer cell lines.

When cisplatin-resistant NSCLC cell lines with high levels of hyperactivated PARP1 and PAR were exposed to each of two distinct PARP inhibitors, the cell lines initiated a cellular process that resulted in their death. Levels of PAR were more predictive of response to PARP inhibitors than were levels of PARP1 itself, suggesting that PAR may be an effective biomarker of response to cisplatin, according to Kroemer.

He and his colleagues then examined whether treatment with a PARP inhibitor affected the growth of tumors in mice xenografted with human NSCLC cell lines. They found that treatment significantly slowed tumor growth.

"Our data show that in most cases, cisplatin resistance is linked to stereotyped biochemical changes in cancer cells that render them vulnerable to PARP inhibitors," said Kroemer. "This has clear implications for new treatment regimens and for developing biomarkers of response to cisplatin. We are following up these exciting clinical possibilities in our laboratory."


'/>"/>

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

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. New Stool Test Might Aid in Early Detection of Colon Cancer
3. Study reveals how cancer drug causes diabetic-like state
4. How a cancer drug leads to diabetes
5. You Survived Cancer: Now Pay Attention to Your Overall Health
6. New drug prevents spread of human prostate cancer cells
7. Eliminating the good cholesterol receptor may fight breast cancer
8. Taller, Heavier Women May Face Higher Ovarian Cancer Risk
9. Experimental Chemo Combo for Colon Cancer Disappoints
10. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
11. Targeted therapeutics for colon cancer to be presented at AACR meeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/21/2017)... ... July 21, 2017 , ... The Wettstein Agencies, ... communities in the greater Denver region, is announcing a charity drive to help ... rare kind of epilepsy. , Until a few months ago, Dominik was a ...
(Date:7/21/2017)... Helena, AL (PRWEB) , ... July 21, 2017 ... ... that offers insurance assistance and financial planning services to communities in the greater ... that promises to provide resources to underprivileged young people in the region. , ...
(Date:7/21/2017)... ... July 21, 2017 , ... ... Theater of Witness , was awarded a $300,000 grant from The Pew ... fosters empathy, comfort with ambiguity and the recognition of one’s own limits among ...
(Date:7/21/2017)... ... ... The Margarian Law Firm has filed a class action lawsuit ... containing no ginger. Dr. Pepper produces the “Canada Dry” brand of ginger ale products. ... Dry Ginger Ale claims on its bottle that it is made from real ginger. ...
(Date:7/21/2017)... ... July 21, 2017 , ... MedMatchPlus+ has launched a ... acceptance to a residency in a United States hospital. Being accepted into a ... , According to data released by the ECFMG®, every year, 50 percent of ...
Breaking Medicine News(10 mins):
(Date:7/14/2017)... 13, 2017 It should come as no surprise ... is in the midst of a crippling opioid epidemic. According ... the number of overdose deaths from opiate-based medications has quadrupled, ... a million dead from 2001 to 2015". During this time, ... has similarly quadrupled, drawing a compelling link between prescription and ...
(Date:7/12/2017)...  Eli Lilly and Company (NYSE: LLY ) ... resolve pending patent litigation in the U.S. District Court for ... the Cialis ® (tadalafil) unit dose patent. This patent ... part of the agreement, Cialis exclusivity is now expected to ... "The unit dose patent for Cialis is valid and infringed ...
(Date:7/11/2017)...  Dr. Echenberg, founder of Echenberg Institute, is announcing a new safe ... from painful intercourse and other painful pelvic pain conditions such as pelvic ... ... ... Florida -based start-up company, VuVatech LLC, fills a void in the ...
Breaking Medicine Technology: