Newswise — Annually, over 40,000 females succumb to ovarian cancer in Europe. Ovarian cancer exhibits extensive genetic diversity, rendering its investigation and management highly challenging. The outlook for ovarian high grade serous carcinoma (HGSC), a specific form of this cancer, is notably bleak. Merely under 40% of individuals diagnosed with this subtype survive beyond five years.
The scientists successfully categorized HGSC tumors into three clusters based on genomic alterations. These clusters exhibit variations in intracellular signaling pathways, tumor growth patterns, and treatment response. These findings hold the potential to enhance precision in therapies and provide improved outcomes for HGSC patients.
"Previous research has failed to identify universally recognized subgroups of HGSC tumors that would allow for targeted treatments similar to those in breast cancer, for example. Our study represents a significant advancement in the identification of effective targeted therapies," explains Professor Sampsa Hautaniemi, an expert in Systems Biology from the University of Helsinki.
Three signalling pathways
The scientists examined genomics data from the DECIDER project, which involved the analysis of cancer tumors obtained from 148 HGSC patients treated and recruited at Turku University Hospital. They categorized the tumors into three evolutionary states—evolving, maintaining, and adaptive—depending on their stage of development. This classification was determined by observing the spread pattern of the tumors and their progression in metastatic sites. The cancer populations within each group consisted of a combination of genetically distinct or clonal cells. Some combinations continued to evolve in metastases, while others remained unchanged.
The researchers identified signalling pathways characteristic of each tumour group, which make these tumours biologically distinct.
"Numerous targeted drugs are currently being clinically employed for many of these subgroups. Our study has shown the significance of a specific signaling pathway, PI3K/AKT, for certain patients. Although the importance of this pathway has been recognized, it was previously unclear which individuals are most likely to respond to treatment targeting this pathway. With our findings, we can now more effectively identify the subset of patients who are likely to benefit from such targeted treatment," explains Jaana Oikkonen, a Postdoctoral Researcher from the University of Helsinki
Tumour evolution should be investigated
The study takes a tumor evolution perspective, focusing on the development and spread of tumors into new metastatic sites. This approach is of significant importance in HGSC research, as the existing knowledge is predominantly derived from studies with limited sample sizes or patient numbers. By adopting this approach, the study aims to contribute to a broader understanding of HGSC and provide insights that can overcome the limitations of previous research.
"The dataset we analyzed is one of the largest, if not the largest, to date in terms of HGSC tumor samples. This serves as further evidence of the remarkable research capabilities in Finland, despite our relatively small population," Hautaniemi remarks.
"Our findings provide structure amidst the genomic complexity of HGSC. With this new knowledge, the entire research field can progress more rapidly, facilitating targeted therapies. Nevertheless, there is ongoing work to be done. Further research is currently underway to determine the most efficient method of classifying patients into the three identified groups," explains Alexandra Lahtinen, a Postdoctoral Researcher from the University of Helsinki.
The outcomes of the collaborative study conducted by the University of Helsinki, Turku University Hospital, HUS Helsinki University Hospital, the University of Turku, and the University of Copenhagen were published in the Cancer Cell journal in May.
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