Real-time therapy tailoring for ovarian cancer patients

A functional precision oncology study conducted by a research team from Finland highlights systematic drug response differences across ovarian cancer subtypes and highlights patient-specific drug regimens that could help to optimize therapies to individual patients in the future.

Epithelial ovarian cancer is the most common type of ovarian cancer. It is also the most lethal gynaecological cancer in the developed countries with a relatively poor survival rate that has not improved much over the last 30 years.

A research team led by researchers from the Institute for Molecular Medicine Finland, the Faculty of Medicine, University of Helsinki, and the Helsinki University Central Hospital, has developed novel approaches for functional cancer precision medicine for more than 10 years.

Their latest study, just published in the British Journal of Cancer, demonstrates that treatment selection based on results from drug sensitivity testing of patients' cells can be clinically useful in patients with rare ovarian cancers.

The researchers tested the effects of more than 500 candidate drugs on the patient cells from 13 patients with different subtypes of epithelial ovarian cancers. Tested compounds included both approved cancer drugs and emerging or investigational cancer drugs.

The results showed that the ovarian cancer subtypes had different overall drug response profiles, with low-grade serous carcinomas responding better to targeted inhibitors than high-grade serous carcinomas. 

“Our functional precision oncology approach combines genomic and transcriptomic profiling with comprehensive drug sensitivity testing of patient cells in a clinically actionable time frame,” said the first author of the study, Dr. Astrid Murumägi, a Senior Researcher at Olli Kallioniemi’s group at FIMM, University of Helsinki-

“In addition to understanding to what extent do the different ovarian cancer subtypes differ from each other, our aim was to identify novel therapeutic opportunities for individual patients.”

The results of the study were promising. The researchers were able to establish representative patient-derived cells in a clinically actionable time-frame for all patients.

Translation to clinical treatment was possible in one of the cases for a patient with metastatic low-grade serous ovarian cancer. This patient had an oncogenic fusion gene CLU-NRG1 and was unresponsive to a conventional chemotherapy. She was treated with multiple therapies selected based on the functional drug response profiling results. The initiation of each of these therapies led to positive responses and eventually kept the disease under control for over 5 years. 

“This study brings personalized medicine closer to reality in ovarian cancer. Drug sensitivity testing may particularly benefit patients with rare subtypes of ovarian cancer,” said Chief Physician of Gynecological Oncology Mikko Loukovaara from the HUS Women’s Hospital.

The researchers concluded that functional precision medicine is expected to significantly expand the actionability of the current, mostly genomics-based personalised medicine approaches, and help in drug repositioning to new indications.

Original publication:

Murumägi, A., Ungureanu, D., Khan, S. et al. Drug response profiles in patient-derived cancer cells across histological subtypes of ovarian cancer: real-time therapy tailoring for a patient with low-grade serous carcinoma. Br J Cancer (2022).