Camilla Krakstad
The Bergen Gynecologic Cancer Research Group.
About the research group
Professor Camilla Krakstad is PI for the Bergen Gynecologic Cancer Research Group. She did her PhD at the University of Bergen in 2005 and has a broad background in cell biology, with specific training in translational cancer research. In 2013 she received funding from the Trond Mohn Research Foundation and established her own research portfolio focusing on model systems for gynecological cancers. She was appointed associate professor at the Department of Biomedicine in 2015, and full professor at the Department of Clinical Science in 2017. Krakstad has been PI or co-investigator on several national and international grants and has built a solid international network. She has contributed to more than 140 publications over the last decade focusing mainly on endometrial cancer (EC).
Brief group presentation and history
The group has a long tradition of translational research in gynecologic cancers, with a primary focus on molecular characterization of various cancer stages, functional studies and model systems, identification of new diagnostic (bio)markers and preoperative imaging, the latter in collaboration with Professor Haldorsen’s group. Headed by the late Professor Helga B. Salvesen until 2016, the group has been an integrated part of the Women’s Clinic (KK) at Haukeland University Hospital and the Department of Clinical Science, UiB for more than two decades. The research group is deeply involved in biobanking from all gynecological malignancies, in close collaboration with clinicians. Professor Krakstad joined the research group as a researcher in 2010 and has led the group since 2016.
Research focus
The research group has a strong focus on better understanding of endometrial and cervical cancer development, molecular subtypes and mechanisms that can be exploited for future improved treatment. The group performs molecular profiling of cervical and endometrial cancers, including in recent years also a stronger focus on single-cell phenotypes and clonal evolution. To enable more relevant studies on mechanisms of cancer growth and metastasis, endometrial cancer organoid models have been established from all histological grades and subtypes.
Subprojects
1. Identification and implementation of biomarkers for endometrial cancer
Improving current diagnostic protocols by integrating available data, performing genetic profiling and identifying new markers that can better stratify patients to correct risk groups, preferentially pre-operatively. The MOMATEC2 study, a phase 4 implementation trial for validation of ER/PR status to stratify for lymphadenectomy in endometrial cancer, is ongoing and also includes collection of quality-of-life data from women treated for endometrial cancer.
2. Generation of relevant model systems for endometrial cancer
Organoid models of endometrial cancer have been developed by the research group and extensively characterized (histology, genetics and biomarker expression). Metastatic potential of models from aggressive subtypes is confirmed in orthotopic mice models (O-PDX). The group is prospectively building a model biobank. The models are used in projects exploiting different library screening and barcoding techniques in collaboration with groups at DFCI/Harvard and The Broad.
Translational, clinical, and societal importance
- MOMATEC2 trial on ER/PR for clinical implementation.
- Her2 paper for endometrial cancer Br J Cancer 2018, PMID: 29169184 has informed clinical trials for Her2 targeted therapy in EC and has gained recent attention due to the relevance and introduction of ADC-based therapies. A paper on this has been accepted by Jama Oncol (2024).
- For societal importance, see paper: Fonnes T, Telle IO, Forsse D, Falck R, Trovik J, Haldorsen IS, Krakstad C. Cancer awareness in the general population varies with sex, age and media coverage: A population-based survey with focus on gynecologic cancers. Eur J Obstet Gynecol Reprod Biol 2021, PMID: 33161211.
Future perspectives from 2024
The group will continue to focus on improving treatment for patients with gynecological cancers, with a special focus on endometrial cancer. They will continue their strong international collaborations and focus on identification of cellular and genetic mechanisms leading to metastatic spread.
Results from the CoE period 2013-2024
Most important results
1. Generation of relevant model systems for endometrial cancer
The group established EC organoid models from all histological grades and subtypes that mimic key features and heterogeneity of endometrial tumors. Together with O-PDX models, this comprises a platform with broad applications in experimental and preclinical research. The striking prognostic potential of the identified gene signature is interesting and supports the strong clinical relevance for future drug testing studies in EC organoid models.
2. Genetic and phenotypic profiling of endometrial cancer
The group has shown that paired primaries and metastases from several dozen ECs spread through a strong bottleneck, suggesting evolutionary selection. Tumors revealed cellular heterogeneity in low stage endometrioid tumors and identified low epithelial vimentin expression in low-stage endometrial cancer with high-risk of recurrence. Integrated genomic analyses of cervical squamous cell carcinomas identified two therapy-relevant subtypes.
3. Identification of biomarkers for endometrial cancer
- MSH6 is an independent prognostic marker in an MMR-D classifier in endometrial cancer.
- PD-L1 and PD-1 are frequently expressed in endometrial cancer with similar expression patterns across MSS and MSI tumors, but in metastatic lesions, expression is intravariable compared to primary tumors.
- High HER2 protein is significantly associated with features of aggressive disease and increased mRNA ERBB2 levels.
4. Implementation of biomarkers in clinical practice
- Self-reported QOL-data for patients with endometrial cancer show that patients receiving adjuvant chemotherapy have a higher risk of experiencing long-term neuropathy, lymphedema, and fatigue and inferior physical function compared to patients undergoing LNS alone or no LNS. Further striving to individualize adjuvant treatment is more pressing than adopting new surgical staging techniques.
- The interim analyses of MOMATEC2 data show that preoperative stratification by imaging and histological assessment permits a reduction in lymphadenectomy to around 50%, and this is achievable without an increase in recurrences at 3 years.
Most important papers
- Krakstad C et al. Frequency of HER2 low in Endometrial Cancer. Jama Oncol 2024 (accepted).
- Lien HE et al. Single-cell profiling of low-stage endometrial cancers identifies low epithelial vimentin expression as a marker of recurrent disease. eBioMedicine 2023. PMID: 37146405.
- Berg HF et al. Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value. Br J Cancer 2022. PMID: 36482191.
- Forsse D et al. Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study. Am J Obstet Gynecol 2022. PMID: 34400137.
- Berg HF et al. Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis. Commun Med (Lond) 2021. PMID: 35602206.
- Halle MK et al. HER2 expression patterns in paired primary and metastatic endometrial cancer lesions. Br J Cancer 2018. PMID: 29169184.
- Forsse D et al. Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer. Gynecol Oncol 2021. PMID: 33317908.
CCBIO significance
"CCBIO provides a platform for collaborations, discussions and education between researchers with complementary interests and background. For the younger researchers, the research school has been instrumental in bridging groups as well as inspiring and educating new talents. Available infrastructure has enabled development of new research projects and added valuable new possibilities to explore biomarkers in cancer."