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Research Highlight | Sep 29, 2016

Ovarian cancer: Mapping the clonal spread

Dr. Shah
Dr. Sohrab Shah

A team of B.C.-based, TFRI-funded scientists are breaking new ground with a recent study that tracked the clonal spread and 
intraperitoneal mixing of high-grade serous ovarian cancer (HGSOvCa), the deadliest subtype of the disease.

Their findings, published in Nature Genetics (July 2016), mapped the different patterns of metastatic spread in the peritoneal cavity of women with HGSOvCa. At least two divergent modes of intraperitoneal metastasis were identified, highlighting the interplay between genomically diverse clones and their migratory potential prior to treatments in this subtype of ovarian cancer.

 As many as 80% of  (HGSOvCa) patients suffer relapse after initial response to treatment. It is characterized by widespread and early intraperitoneal spread to organs, and the patients account for nearly 70% of all ovarian cancer cases.

The present study provided valuable information about the composition of the cancer cell groups in metastatic cancers. It was found that many different types of cancer cells make up a patient’s tumour, which may explain why some cells are eradicated by treatment while others become resistant, eventually resulting in the patient's relapse. HGSOvCa also appears to have the unique ability to metastasize prolifically throughout the abdomen, which often results in patient death.

These findings suggest that some cancer cells may have had pre-existing properties of resistance before a patient begins treatment. Understanding this could lead to women being given a more aggressive, multi-treatment approach at the beginning of their therapy in an effort to prevent patient relapse, versus waiting until the cancer has already returned. Future research will help to define cell migration maps in more patients, with a focus on ascertaining which cells are resistant to treatment, and enabling researchers to create predictive tools to better inform future care for women with this lethal type of ovarian cancer.

Study: Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer

 Authors: Andrew McPherson, Andrew Roth, Emma Laks, Tehmina Masud, Ali Bashashati, Allen W Zhang, Gavin Ha, Justina Biele, Damian Yap, Adrian Wan, Leah M Prentice, Jaswinder Khattra, Maia A Smith, Cydney B Nielsen, Sarah C Mullaly, Steve Kalloger, Anthony Karnezis, Karey Shumansky1, Celia Siu, Jamie Rosner, Hector Li Chan, Julie Ho, Nataliya Melnyk, Janine Senz8, Winnie Yang, Richard Moore, Andrew J Mungall, Marco A Marra, Alexandre Bouchard-Côté, C Blake Gilks, David G Huntsman, Jessica N McAlpine, Samuel Aparicio & Sohrab P Shah.

Funding: This work was funded by the BC Cancer Foundation. In addition, the groups of S.P.S. and S.A. receive operating funds from the Canadian Breast Cancer Foundation, the Canadian Cancer Society Research Institute (grant 701584), the Terry Fox Research Institute (TFRI), Genome Canada/ Genome BC (173-CIC and 177-EVO), the Canadian Institutes of  Health Research (CIHR) (MOP-115170, MOP-126119, and FDN-143246), a new investigator grant to J.N.M. (MSH-261515), and a TFRI new investigator award to S.P.S. S.P.S. and S.A. are supported by Canada Research Chairs.

TFRI LInks, Fall 2016