Professor Camilla Krakstad has her background from research on signal transduction, and during her PhD she studied cAMP signaling in apoptotic cell death in both normal and cancer cells.
Professor Krakstad is leader of the the Bergen Gynecologic Cancer Research Group, which focuses on identifying molecular alterations underlying initiation and development of gynecologic cancers. The gained molecular knowledge from their studies will contribute to improved future clinical trials on molecularly targeted therapies. To improve disease detection and diagnosis, the aim is to identify and validate both imaging and molecular biomarkers, in close collaboration with the clinic.
- The MOMATEC2 study (NCT02543710), a phase 4 implementation trial, is ongoing for validation of ER/PR status to stratify for lymphadenectomy in endometrial cancer.
- Molecular profiling of paired primary and metastatic endometrial cancer is performed in close collaboration with Professor Beroukhim, The Broad Institute, USA (CCBIO affiliated).
- Comprehensive profiling of genetic alterations linked to molecular subtypes of cervical cancer is ongoing in collaboration with Professor Ojesina, UAB, USA.
- Molecular biomarkers and genetic data are combined with preoperative imaging parameters derived from PET-CT and/or MRI. This project is in collaboration with Professor Ingfrid Haldorsen and provides exciting information on tumor characteristics and potential new imaging-based preoperative biomarkers.
- There is a lack of good model systems for endometrial cancer. The Gynecologic Cancer Research Group is constantly working to develop better 2D and 3D cell models in parallel with developing relevant mouse models. Both imaging and molecular biomarkers are explored in endometrial cancer orthotopic mouse models.
The team identified Asparaginase-like protein 1 (ASRGL1) as an independent prognostic biomarker in endometrial carcinoma and found that expression of ASRGL1 is lost in metastatic lesions. Also, using specimens from the multicenter study MOMATEC1, the group found that ASRGL1 expression in curettage specimens independently predicts lymph node metastasis in endometrial carcinoma. They identified PIK3CA amplification to be associated with aggressive disease, suggesting that PIK3CA amplification might be a surrogate marker for the serous-like somatic copy-number alteration–high subgroup of endometrial cancer. Continuous work to improve mouse models for endometrial cancers also resulted in development of a new orthotopic model with controllable estrogen exposure. This is an excellent in vivo tool to further explore endocrine drug regimens and novel endocrine drug targets for EC.
The MOMATEC2 study is ongoing and the international inclusion of patients has been well established. An interim analysis has been performed for the Momatec2 study, and a report has been prepared and will be circulated to participating centers in 2019. To further explore aspects of hormone regulation in EC, the group investigated the relation between blood steroids and aggressive disease. Several plasma steroids were established as promising biomarkers. The association between increased estradiol levels and a high percentage of visceral fat indicates a larger contributor to estradiol production compared to subcutaneous fat in this population.
Current challenges in the field
With a tight link between endometrial cancer and obesity, the incidence of endometrial cancer is expected to rise. Identifying specific patient populations that are likely to respond to therapy is therefore even more important.
CCBIO focus in the coming years
The group commends CCBIO’s large network that allows close collaborations between research groups with similar focus but different expertise, and will use this to continue developing their collaboration with groups in the CCBIO family. They also aim at establishing new collaborations with CCBIO’s associated international investigators. They will continue to use the CCBIO research school to train their PhD candidates and the regular seminars and annual symposium to interact and develop collaborations and future projects.