“Shielded” Ovarian Cancer Cells May Survive Chemotherapy

Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer.

Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer. This could help explain why the disease can be difficult to treat, according to new research published in Oncogene on June 28.

The study, funded by Cancer Research UK, aimed to find out whether it is the chemotherapy itself that causes anti-cancer drug resistance to build in the body – similar to resistance to antibiotics – or if cells that are shielded against cancer treatment grow as part of the initial tumor and are already lying dormant before chemotherapy begins.

Often ovarian cancer can be hard to treat with treatment failing after women initially responded well. The number of women surviving beyond five years is less than 35 per cent.

The researchers compared the characteristics of cell lines from the tumor at the time of diagnosis to cell lines from the same patients once the disease had been treated and become resistant.

Dr. James Brenton, Researcher, Functional Genomics of Ovarian Cancer, Cambridge Research Institute

Dr. James Brenton, study author from the Cancer Research UK’s Cambridge Research Institute, said:

“Ovarian cancer is notoriously hard to treat. Women usually respond well to their first round of chemotherapy with the disease apparently completely removed.  But unfortunately many go on to relapse within six to 24 months. Until now we haven’t known whether they are becoming resistant to the treatment or whether the cells that don’t respond to treatment re-grow the tumour.

By examining the characteristics of ovarian tumours we now think that cells resistant to chemotherapy grow as part of the tumor. This means that when patients have treatment, cells that respond to chemotherapy are destroyed but this leaves behind resistant cells which then form another tumor of completely resistant cells. This seems to explain why successful treatment for relapsed patients is difficult. What needs to be developed now is a therapy designed to target the resistant cells.”

Dr. Lesley Walker, director of science information at Cancer Research UK, said:

“Discoveries like this help to tell us why chemotherapy stops working for some ovarian cancer patients. We hope it will lead to new ways to tackle the disease and increase the number of women that survive this cancer that can be so hard to cure. The next step will be to develop treatment tailored to fight the resistant cells.”

Sources:

• “Shielded” ovarian cancer cells may survive chemotherapy, Press Release, Cancer Research U.K., June 28, 2010.

• SL Cooke, CKY Ng, N Melnyk, et. al.  Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. Oncogene , 28 June 2010, doi:10.1038/onc.2010.245 (epublished ahead of print).

Pattern of Genetic Faults Could Predict Whether An Ovarian Cancer Patient Will Respond to Common Chemo Drugs

“… A pattern of genetic defects in tumours could indicate whether ovarian cancer patients will respond to common chemotherapy drugs before treatment starts, reveals a Cancer Research UK study published in the Proceedings of the National Academy of Sciences … The researchers studied patterns of gene expression that indicate high levels of abnormal chromosomes or chromosomal instability (CIN) in cancer. …Patients with high levels of the CIN gene pattern were more resistant to paclitaxel.  Crucially, patients with high levels of CIN responded well to carboplatin – another commonly used ovarian cancer drug.  In contrast, tumours with low levels of CIN were resistant to carboplatin but responded to paclitaxel. …”