Edited by Tiia Pelkonen & Mila Hyytinen
High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer. HGSOC tumours often consist of several heterogeneous cell populations with a large number of mutations. This genetic variability makes it difficult to find drugs that would kill all the cancer cells, and to which the cells would not become resistant during treatment. For more on heterogeneity in ovarian cancer, see also our previous blog post on single-cell studies.
To improve the efficacy of HGSOC treatment, researchers from the HERCULES project at Turku University Hospital, University of Helsinki and University of Turku have studied the use of circulating tumour DNA in finding personalised treatments for the disease. In this post Johanna Hynninen, MD, PhD, from Turku University Hospital and Jaana Oikkonen, PhD, from University of Helsinki tell us about the background and progress of our ctDNA research in ovarian cancer.
What is circulating tumour DNA and what can it tell us?
Cancer cells release circulating tumour DNA (ctDNA) into the bloodstream, which can then be measured from a blood sample using sufficiently sensitive methods. This can provide us with up-to-date information on the genetic composition of the tumours within the body.
In recent years, cancer research has focused on individual cancer treatments, which use genetic analyses of the tumour to find targeted therapies that would suit each patient and their tumour. To achieve this, representative samples of the tumours are needed.
A large tumour may sometimes consist of several different cell populations, and metastases may contain cell populations that are different from the original tumour. As the treatment progresses, drug-resistant cells may take over and the tissue sample taken before the treatment may no longer represent the current tumour, if the cancer comes back.
By comparing different samples from tumour tissue, ascites (fluid that often accumulates into the abdominal cavity during ovarian cancer) and ctDNA from blood samples, the researchers aim to find the best means to address the causes of drug resistance. The use of ctDNA analytics helps to acquire up-to-date information about mutations in the tumours and to find new drug options if the disease recurs, without the need to take invasive tissue biopsies.
Can ctDNA be used in treatment planning?
The possibilities to use ctDNA in diagnostics and follow-up has caused great excitement among cancer researchers in the last few years, and commercial ctDNA tests are already on the market. In the case of lung cancer, for example, ctDNA is already being used to guide the patient’s clinical treatment, but the usefulness of the method has not yet been established for ovarian cancer. Before using expensive tests in the treatment of patients, it must be certain that the blood sample provides a highly reliable representation of the patient’s tumour.
Our research aims to find out if the treatment of a recurring ovarian cancer can be planned on the basis of tissue samples taken during surgery or would a more recent ctDNA or ascites sample be a better option. Another aim is also to identify, at an early stage, those patients whose disease will recur rapidly, so that they could be followed-up more closely.
What has been accomplished so far and what’s next?
We have already developed and used a ctDNA analysis workflow to detect alterations that can provide targets for treatments in more than 500 cancer-related genes and analysed 78 ctDNA samples from 12 ovarian cancer patients before, during and after the treatment. DNA alterations associated with clinically available drugs were detected in 58% of the patients.
The treatment of one patient was already tailored successfully based on the results. For the other patients the results may be useful if their cancer relapses in the future. These preliminary results were published in a JCO Precision Oncology journal article. Since this publication, we have collected much more data, which is currently being analysed.
These results provide evidence that circulating tumour DNA could be used to guide clinical decisions also in ovarian cancer and that analysing ctDNA samples collected during the treatment could identify poor-responding patients after first cycles of chemotherapy.
As the HERCULES project is drawing to an end, the research into ctDNA in ovarian cancer continues in a new project called DECIDER. You can read more about the project at DECIDER website.
Funding for the ctDNA research has been provided by the European Commission (Grant Agreement 667403 for HERCULES), Academy of Finland and Sakari Alhopuro foundation.