Navigation Links
Cisplatin-resistant cancer cells sensitive to experimental anticancer drugs, PARP inhibitors

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
American Association for Cancer Research

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:
(Date:12/1/2015)... TX (PRWEB) , ... December 01, 2015 , ... Dr. ... of Vitenas Cosmetic Surgery, has been named by MedEsthetics magazine as the Best Single ... of the best among the many elite aesthetic physicians honored by the industry publication. ...
(Date:12/1/2015)... ... 2015 , ... December 1, 2015 -- InstantLabs is adding ... product line of food safety and seafood fraud prevention tools. , The new ... InstantLabs to offer fast, reliable species identification for the four most popular salmon. ...
(Date:12/1/2015)... ... 2015 , ... It’s official: Tattoo taboo is a thing of the past. ... Millennials (a whopping one in three aged 18 to 25 is inked). As tattoos ... their ink. In fact, RealSelf , the world’s largest community for learning and ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... of adjunctive imaging is the focus of numerous abstracts accepted for presentation here, ... 4, 2015. Nine abstracts highlight the use of Volpara Solutions’ quantitative breast ...
(Date:12/1/2015)... (PRWEB) , ... December 01, 2015 , ... ... , Visage Imaging Inc. (“Visage”), a wholly owned subsidiary of Pro Medicus Ltd. ... results enhancements at the Radiological Society of North America (RSNA) 2015 annual meeting ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... BANGALORE, India and PITTSBURGH ... TASE: MYL) today announced that it expects to be ... developing country markets funded by international donors, TLE400 (Tenofovir ... Efavirenz 400 mg) for $99 per patient, per year. ... to develop TLE400. The significantly reduced price could generate ...
(Date:12/1/2015)... , Dec. 1, 2015 Breg, Inc ... services, announced today that it has been awarded three ... Members served by Novation will have access to improved ... bracing products and soft goods dedicated to advancing orthopedic ... The aging U.S. population, rising prevalence of chronic ...
(Date:12/1/2015)... N.J. , Dec. 1, 2015 ... against HIV/AIDS, Johnson & Johnson (NYSE: JNJ ... its Janssen Pharmaceutical Companies to significantly reduce the ... who make up 74 percent of new HIV ... Announced on World AIDS Day, these new initiatives ...
Breaking Medicine Technology: