The Histone Methyltransferase EZH2 Is a Therapeutic Target in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
This week we profile a recent publication in The Journal of Pathology from the laboratory
of Dr. David Huntsman at the BC Cancer Research Centre.
Can you provide a brief overview of your lab’s current research focus?
The lab is focused on using research to improve management of gynecological cancers, with a focus on developing therapies and prevention strategies that are shaped by the biology of the cancer. In the case of small cell carcinoma of the ovary, hypercalcemic type, we were able to discover the genetic changes that characterize this tumour type. We are now taking efforts to understand how these genetic changes alter the biology of the tumour and develop treatments that are informed by that altered biology.
What is the significance of the findings in this publication?
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal ovarian cancer in young women due to lack of effective treatment. Our current study suggests that SCCOHT tumor cells need the activity of an enzyme called EZH2 for their survival. This enzyme adds methyl groups to the dedicated site of histones, a group of proteins that maintain the proper structure of DNA, and thereby controls which genes to turn on or off. Two EZH2 inhibitors, both in various clinical trials, displayed robust preclinical activities against SCCOHT tumor, which highlights the great potential of rapidly translating our findings into clinic trials to help patients with SCCOHT.
Briefly, what are the next steps for this research?
We are working to identify “molecular markers” to predict the response of SCCOHT tumors to EZH2 inhibitors. By seeing which markers are present in patients, we can determine the SCCOHT patients that will benefit from the treatment. The danger of treating cancer patients with a single drug is the almost inevitable development of resistance to that drug. For this reason, we are working to develop strategies that can improve the efficacy of EZH2 inhibitor treatment alone.
This project was supported by:
This study was supported by funds from Canadian Cancer Society Research Institute, the National Institute of Health, the Terry Fox Research Institute Initiative New Frontiers Program in Cancer and the British Columbia Cancer Foundation.