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:10/13/2017)... , ... October 13, 2017 , ... The American Board ... become its next President and Chief Executive Officer, succeeding Dr. James C. Puffer upon ... beginning July 1, 2018 until Dr. Puffer’s retirement at the end of 2018. Upon ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... PurhealthRX ... CBD Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will ... and providing a CBD form that can be easily incorporated into liquid products, while ...
(Date:10/13/2017)... ... October 13, 2017 , ... Lori R. Somekh, founder ... of ElderCounsel, a national organization of elder law and special needs planning attorneys. “Membership ... rules. It also provides a forum to network with elder law attorneys nationwide,” said ...
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that covers care ... have a waiver for care if the client has a cognitive impairment diagnosis. ... for care, is often waived, so the benefits from their insurance start immediately,” said ...
(Date:10/13/2017)... ... 2017 , ... Ellevate Network, the leading network for professional women, brought together ... equality at their inaugural Summit in New York City in June. The event was ... of over 3 million. To watch the Mobilize Women video, click here . ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... CHICAGO , Sept. 28, 2017 Hill-Rom ... quarter 2017 earnings conference call and webcast on Friday, ... 8:00 a.m. (EDT) and ending at approximately 8:30 a.m. ... to discussing the company,s 2017 financial performance and guidance ... growth opportunities, initiatives to enhance operational performance, and long-range ...
(Date:9/27/2017)... , Sept. 27, 2017  Commended for their devotion ... notable awards. Ranked as number one in the South Florida ... time in Inc. 5000 yearly list, the national specialty pharmacy ... Armando Bardisa will soon be honored by SFBJ ... Set to receive his award in ...
(Date:9/25/2017)...   Montrium , an industry leader in ... IQPC Trial Master Files & Inspection Readiness Conference ... Clinical Services has selected eTMF Connect ... EastHORN, a leading European contract research organization (CRO), ... to enable greater collaboration with sponsors, improve compliance ...
Breaking Medicine Technology: