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Ovarian Cancer

Scientists identify cause for chemotherapy resistance in ovarian cancer.

Scientists working at the Peter MaCallum Cancer Centre (Peter Mac) in Melbourne, Australia have discovered a possible cause why the most common type of ovarian cancer often becomes resistant to chemotherapy. The findings were published in the journal Cancer Research*.

Ovarian cancer kills more than 4000 women in the UK every year. High Grade Serous Cancer is the most common type of ovarian cancer, and accounts for around 65% of these deaths.  Chemotherapy for the HGSC type of ovarian cancer can be very effective to begin with, but too often these tumours stop responding to chemotherapy over time.

With a grant from AICR, Dr Prue Cowell and Dr David Bowtell have identified a gene that appears to play an important role in HGSC tumours becoming resistant to treatment.

 “We were interested in identifying the molecular changes that occurred in a tumour between the time when a woman was first treated, with surgery and chemotherapy, and the time when the tumour recurred and eventually became resistant to chemotherapy.” explains Dr David Bowtell, Head of the Cancer Genomics Program at Peter Mac, who led the study.

22 women with the HGSC type of ovarian cancer donated samples of their tumours before and after they were treated with chemotherapy.  When the researchers studied these samples they found that the genes within the cancer cells had changed greatly in the time between the two sets of samples being taken. The amount of change was greatest in the tumours that had initially responded well to chemotherapy treatment, but later became resistant to it. The genetic change that happened most often caused a reduction in the levels of a protein called LRP1B. In laboratory studies, LRP1B helps stop cancer cells growing. 

Dr Prue Cowin, who performed a large part of the research, said “We were surprised by how much variation we found between the tumour samples that we collected during surgery, and the samples that were collected after the tumours returned. This provides the cancer with many ways to become resistant to chemotherapy, and may help explain why it has been so difficult to make progress with this disease.”

 “Resistance to chemotherapy is a huge problem for many people affected by cancer and an enormous challenge for cancer researchers to solve” said Dr Gwen Wathne, Science Communications Manager at AICR. “We are delighted to have funded this study, which reveals one of the reasons why this happens in the most common type of ovarian cancer.  We hope that this line of research will one day help doctors predict which ovarian cancers are likely to become resistant to chemotherapy, leading to an improvement in treatment for the estimated 225,000 (7000 in the UK) women who are diagnosed with the disease worldwide every year.

* Prue A. Cowin et al, LRP1B Deletion in High-Grade Serous Ovarian Cancers Is Associated with Acquired Chemotherapy Resistance to  Liposomal Doxorubicin, Cancer Research, doi: 10.1158/0008-5472.CAN-12-0203


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