Genetic marker for ovarian cancer treatment
Tumour DNA sequencing enables doctors to customise treatment for individual patients based on their unique genetic makeup. This is called precision medicine in which genetic markers can help predict the most effective drugs to kill tumour cells for specific patients. As a result, precision medicine may reduce the cost and time of treatment, and avoid the side effects from taking unnecessary drugs.
Ovarian cancer is the seventh leading cause of cancer deaths among women in Hong Kong. Even with chemotherapy, the recurrence rate is 70-80 per cent in late-stage patients.
Recent research by Professor Annie Cheung (Croucher Senior Medical Research Fellowship 2014) and Dr Lydia Cheung, Assistant Professor, School of Biomedical Sciences, studied tumour DNA sequencing data from over 1,000 ovarian cancer patients. Their team observed PIK3R1 gene loss in 70 per cent of the patients and found the deletion promotes the growth of ovarian tumours through simultaneous activation of two important signalling pathways: AKT and STAT3.
The activated signalling represents a targetable therapeutic approach for ovarian cancer patients with PIK3R1 gene deletion. Drugs inhibiting the two pathways were tested on tumours growing in mice with PIK3R1 loss.
“We successfully showed that the inhibitors are effective against cancer growth, in particular when used in combination,” said Professor Cheung.
This research is the first to pinpoint PIK3R1 gene deletion as a potential marker to guide the combined use of AKT and STAT3 inhibitors in ovarian cancer treatment. These inhibitors are already in clinical trials for multiple tumour types. Incorporating the predictive marker could facilitate the application of the drugs for patients with ovarian cancer.
As the study reveals, PIK3R1 loss is highly common in ovarian cancer, which suggests that the proposed targeted treatment could be applicable to a large proportion of ovarian cancer patients.
The findings have been published in Nature Communications.
Professor Annie Cheung is a Clinical Professor in the Department of Pathology, University of Hong Kong. She is the key pathologist for gynaecological histopathology and cytology in Queen Mary Hospital and Pathologist in Charge of the HKU Cervical Cytology Laboratory, the first pathology laboratory in Hong Kong accredited by the College of American Pathologists. She is also Director (Molecular Pathology) of the University Pathology Laboratory and Chief of Service of Pathology, HKU-Shenzhen Hospital. Professor Cheung received the Croucher Senior Medical Research Fellowship in 2014.
To view Professor Cheung’s Croucher profile, please click here.