Understanding of the mechanisms of drug resistance to dual-agent chemotherapy in ovarian cancer

November 29, 2012

More than half of all patients with ovarian cancer experience recurrent disease and will eventually fail to respond to chemotherapy. The failure of chemotherapy is usually due to the development of resistance to the two main classes of chemotherapy agents used to fight it - platinating agents and taxanes. Now, a study reported in the open-access Journal of Ovarian Research provides novel information that further adds to clinicians' understanding of the mechanisms involved in the development of resistance to dual-agent chemotherapy.

It was not known whether mechanisms of resistance to dual-agent chemotherapy are a combination of single-agent resistance responses or if novel mechanisms arise as a result of combined platinating agent/taxane therapy. Carita Lanner and her team, from Sudbury, Ontario, in Canada, provide evidence to suggest that the latter is true: novel and different changes occur to cause resistance to the dual combination of agents.

Ovarian cancer is the most lethal gynecological cancer, with a 5-year mortality rate of over 50%. A significant contributing factor to the high mortality rate is the development of resistance to chemotherapy regimens. The differences in mode of action and mechanisms of resistance for platinating agents and taxanes are taken advantage of in dual-agent chemotherapy of advanced cancer. Used together, they achieve increased efficacy and progression-free survival in patients. However, combined resistance to both agents may occur, and is more difficult to overcome than single-agent resistance.

Lanner and colleagues set out to investigate if the development of dual agent resistance invokes different mechanisms or is a combination of the mechanisms of resistance that arise upon exposure to single agents. To do this, they developed a set of isogenic ovarian cancer cell lines resistant to either (1) the platinating agent carboplatin, (2) the taxane docetaxel, or (3) a combination of carboplatin and docetaxel. They analyzed changes in gene expression associated with the specified drug resistance in each cell line using microarray analysis.

The team compared the three resistant cell lines to identify shared and different changes in gene expression amongst all three treatments. The analysis showed that the establishment of carboplatin and docetaxel resistance did not share many changes in gene expression. Most significantly, dual-agent resistance appeared to develop from mostly unique changes in gene expression, different from both single carboplatin and docetaxel resistance in the set of isogenic cell lines studied.

Lead author Carita Lanner commented, "These results demonstrate that combined drug resistance is NOT just a combination of changes present in single agent-resistant cells but contains different and new changes. The dual carboplatin-docetaxel resistant cell line will facilitate further investigation into mechanisms underlying the development of dual drug resistance in ovarian cancer."
-end-
Media Contact

Dr Hilary Glover
Scientific Press Officer, BioMed Central
Tel: +44 (0) 20 3192 2370
Mob: +44 (0) 778 698 1967
Email: hilary.glover@biomedcentral.com

Notes

1. Distinct genetic alterations occur in ovarian tumor cells selected for combined resistance to carboplatin and docetaxel Stephen R Armstrong, Rashmi Narendrula, Baoqing Guo, Amadeo M Parissenti, Katherine L McCallum, Stephanie Cull and Carita Lanner Journal of Ovarian Research (in press)

Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy.

Article citation and URL available on request on the day of publication.

2. Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.

3. BioMed Central is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Science+Business Media, a leading global publisher in the STM sector. @BioMedCentral

BioMed Central

Related Chemotherapy Articles from Brightsurf:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.

Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.

Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

Male fertility after chemotherapy: New questions raised
Professor Delb├Ęs, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.

Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.

Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.

Read More: Chemotherapy News and Chemotherapy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.