The group focuses on identifying molecular alterations underlying cancer initiation and progression in gynecologic cancers, aiming to improve knowledge on disease development and progression.
About the group and its research focus
The Bergen Gynaecologic Cancer Research Group is currently headed by Professor Jone Trovik. The group suffered a huge loss early on in 2016 when group leader Helga B. Salvesen passed away. A clear aim in 2016 has been to continue and to further develop the great research Professor Salvesen had established. The group focuses on identifying molecular alterations underlying cancer initiation and progression in gynecologic cancers, aiming to improve knowledge on disease development and progression. In addition, to improve disease detection and diagnosis, the group seeks to identify and validate both imaging and molecular biomarkers in close collaboration with the clinic.
The group’s projects
Together with collaborators at the Broad Institute in Boston, USA, extensive molecular profiling of paired primary and metastatic lesions has been performed, providing increased insight into the underlying mechanisms of disease spread. This is highly motivated by the fact that most cancer deaths are caused by development of metastases, and currently few treatment options are available for metastatic gynecologic cancers. Results were published in Nature Genetics in 2016 (Gibson, Hoivik et al Nat.Gen 2016).
The group has also identified recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers (Holst et al, 2016). The gained molecular knowledge from these studies will contribute to improved future clinical trials on molecularly targeted therapies.
During the past few years, the group has done extensive work to identify more potent biomarkers for gynecologic cancers, with special focus on hormone receptors in endometrial cancer. Recently, they identified Androgen receptor (AR) as a promising biomarker and identified a patient group that might benefit from AR-targeting therapy (Tangen et al, 2016).
The group have launched the MOMATEC2 study (ClinicalTrials.gov Identifier: NCT02543710), a phase 4 implementation trial for validation of ER/PR status as a stratifier for lymphadenectomy in endometrial cancer. The research group has explored the utility of imaging markers like 18F-FDG PET through meta-analysis of literature (Bollineni et al 2016) and in relation to hypoxia (Berg et al 2016). Both imaging and molecular biomarkers are further explored in endometrial cancer orthotopic mouse models, based on cell lines or patient derived xenograft (PDX) models. These models are also used for drug testing and validation of predictive biomarkers. In addition, the research group is an active partner in several international consortiums, resulting in a number of high-impact publications.
The group published the below article with both joint first (Gibson and Hoivik) and senior (Beroukhim and Salvesen) authorship: Gibson WJ, Hoivik EA, Halle MK, Taylor-Weiner A, Cherniack AD, Berg A, Holst F, Zack TI, Werner HM, Staby KM, Rosenberg M, Stefansson IM, Kusonmano K, Chevalier A, Mauland KK, Trovik J, Krakstad C, Giannakis M, Hodis E, Woie K, Bjorge L, Vintermyr OK, Wala JA, Lawrence MS, Getz G, Carter SL, Beroukhim R, Salvesen HB. The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis. Nat Genet. 2016 Aug;48(8):848-55.
Plans for the future
The Bergen Gynaecologic Cancer Research Group will continue to explore genetic alterations linked to progression of endometrial cancer from primary tumor to metastasis, including a higher focus on epigenetic traits. Validation and exploration of single targets will also be included for investigations towards potentially new biomarkers in endometrial cancer. For cervical cancer they have initiated an international collaboration with focus on biomarkers of tumor recurrence and relationship between genomic alterations and clinicopathological phenotypes. Alongside the molecular characterization, they will continue the MoMaTEC2 trial with the goal of implementing molecular biomarkers to identify low risk patients to undergo surgical treatment without lymphadenectomy.
The group will also implement use of an electronic platform collecting extensive patients’ self- reported Quality of Life (QOL) aspects during follow-up of endometrial cancer patients to complement the group’s data. They will continue exploring the endometrial cancer patient-population for biomarkers, with a stronger focus on early detected biomarkers for cancer development and metastatic spread. They plan to perform functional studies related to hormone receptor alterations in endometrial cancer with a goal of exploring effects of drugs that are already approved for other cancer indications.
See the group's PubMed publication list here.