Faculty of Medicine, University of Helsinki
Topic: Characterizing and overcoming chemotherapy resistance mechanisms in ovarian cancer
Time: 13.9.2023 at 15-16
The seminar will be held online (Microsoft Teams) and is open to everyone interested in cancer research.
Chemotherapy resistance is one of the greatest contributors to cancer mortality. A prime example of the impact of our current inability to overcome treatment resistance is seen in ovarian high grade serous carcinoma (HGSC), which is the most common subtype of epithelial ovarian cancer. While 90% of HGSC patients show no clinically detectable signs of cancer after surgery and chemotherapy, tumors become progressively resistant to chemotherapy leading to five-year survival of <40%.
We have established a prospective, longitudinal, multiregion observational study DECIDER (ClinicalTrials.gov identifier NCT04846933) to characterize and overcome chemotherapy resistance in HGSC. In this presentation, I will discuss our latest findings on chemotherapy resistance mechanisms in HGSC, derived from comprehensive patient-level data and ex vivo experiments. Specifically, I will focus on highlighting computational methods that facilitate high-quality data collection from patient samples, HGSC tumor evolution before and during chemotherapy, as well as translating research findings to benefit patients.
Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A, Lauridsen AR, Zhang K, Marchi G, Isoviita VM, Ariotta V, Lehtonen O, Muranen TA, Huhtinen K, Carpén O, Hietanen S, Senkowski W, Kallunki T, Häkkinen A, Hynninen J, Oikkonen J, Hautaniemi S. Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. Cancer Cell. 2023 May 11:S1535-6108(23)00143-5. https://doi.org/10.1016/j.ccell.2023.04.017
Zhang K, Erkan EP, Jamalzadeh S, Dai J, Andersson N, Kaipio K, Lamminen T, Mansuri N, Huhtinen K, Carpén O, Hietanen S, Oikkonen J, Hynninen J, Virtanen A, Häkkinen A, Hautaniemi S, Vähärautio A. Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer. Science Advances. 2022 Feb 25;8(8). https://science.org/doi/10.1126/sciadv.abm1831
Häkkinen A, Zhang K, Alkodsi A, Andersson N, Erkan EP, Dai J, Kaipio K, Lamminen T, Mansuri N, Huhtinen K, Vähärautio A, Carpén O, Hynninen J, Hietanen S, Lehtonen R, Hautaniemi S. PRISM: recovering cell-type-specific expression profiles from individual composite RNA-seq samples. Bioinformatics. 2021 Sep 29;37(18):2882-2888. https://doi.org/10.1093/bioinformatics/btab178
Organizer: FICAN South, Eteläinen syöpäkeskus