Highlights from the first four years
During its first 3.5 years, CCBIO has established promising scientific activities with increased internal and international collaboration as well as industry interaction and is now a well-organized CoE with robust organization and administrative support.
Nine research groups focus on the following core questions: How does the cancer microenvironment interact with and support tumor cells to promote cancer progression, and how can various drivers be blocked? Which novel biomarkers can predict tumor aggressiveness and response to therapy? Studies aim at a refined understanding of tumor complexity and plasticity, especially related to the microenvironment, followed by biomarker and therapy development. To support these aims, basic studies, translational projects, and clinical trials have been established. Integrated studies in ethics and economics are also performed.
The importance of tyrosine kinase Axl
Basic projects have focused on the importance of tyrosine kinase Axl for tumor-stroma interactions. One study demonstrates a unique requirement for Axl-dependent tumor plasticity in aggressive pancreatic cancer (Kirane et al., Cancer Res 2015). Additional findings in the Lorens and Brekken (adjunct professor at CCBIO) groups have formed the basis for clinical translation of Axl inhibitors. Collaborating with BerGenBio, Axl-inhibitor BGB324 is now included in many clinical trials with extensive tissue and liquid based biomarker programs. Importantly, a trial combining BGB324 and immunotherapy has been initiated by CCBIO.
New treatment of aggressive prostate cancer
Kalland´s Group has developed a new in-house prostate tumorigenesis model and initiated new treatment by cryoimmunotherapy of aggressive prostate cancer (NCT02423928). Cell lines from mice tumor tissue revealed a novel autocrine IL6/STAT3 mechanism present in tumor-initiating cells (Qu et al., Cancer Res 2013). By screening biologically active compounds and FDA-approved drugs according to repurposing, compounds with the novel attribute to block WNT/β-catenin and STAT3 signaling and tumor formation in mice have been identified (Qu et al., PNAS 2016). WNT/β-catenin and STAT3 signaling play essential roles in immune evasion, and it is hypothesized that WNT/β-catenin/STAT3 inhibition can be used to enhance immuno-therapy.
Characterization of integrin α11β1
The Gullberg Laboratory concentrate on the extracellular tumor matrix. The team characterized integrin α11β1, which is expressed on subsets of normal and cancer-associated fibroblasts. It was demonstrated for the first time that stromal integrin α11 expression in vivo is important for tumor progress by alterations of stroma stiffness (Navab et al., Oncogene 2015). Generation of novel α11 monoclonal antibodies have been performed, with a potential for translational studies. In collaboration with Reed´s Group, the influence of α11β1 on xenograft tumor growth (breast and prostate cancer) has been studied in mice (Reigstad et al., PLoS One 2016). Gullberg is also collaborating with Johannessen´s group on the role of α11β1 in oral cancer.
Predicting aggressive disease
The Akslen Group concentrates on the tumor vascular system and how novel biomarkers can predict aggressive disease and response to treatment. In one key study, tissue-based microvascular proliferation could be predicted by a 32-gene RNA-based expression signature and linked to 6p21 amplification (Stefansson et al., Oncotarget 2015). Further studies aim to explore novel angiogenesis drivers in this chromosomal region. In a collaborative study with Dr. Watnick, Boston (adjunct researcher at CCBIO), the role of stromal regulators prosaposin and thrombospondin-1 was reported for ovarian cancer progression (Wang et al., Sci Transl Med 2016).
Mapping genomic alterations of cervical carcinoma
The Gynecologic Cancer Group has performed studies on genetic and protein biomarkers in gynecologic cancers. In a landmark paper from 2014, genomic alterations of cervical carcinoma were mapped (Ojesina et al., Nature 2014). Data on novel mutational changes and potential treatment targets in this HPV-related and frequent cancer type were reported. In a study of endometrial cancer, genomic alterations in primary tumors and metastases were presented with novel observations (Gibson et al., Nat Genet 2016).
National study of metastatic melanoma
The Gjertsen Group focus on the design of novel biomarker intense clinical trials at an early stage, using modalities such as single cell protein analysis, liquid biopsy and mass cytometry, with longitudinal data. Several clinical trials with companion biomarker programs have been initiated. In collaboration with Straume´s group and Lorens´ group, a national investigator-based study of metastatic melanoma was initiated, using a combination of anti-Axl treatment (BGB324) and immunotherapy (PD-1) (PI: Straume; NCT02872259).
Straume´s group also reported a role of the tissue based biomarker HSP27 in predicting response to anti-angiogenesis therapy in metastatic melanoma (Schuster et al., PLoS One, 2016).
Influencing national guidelines
In terms of impact on treatment, studies from Akslen´s group on tumor proliferation and lymph node metastases in breast cancer, have influenced new national guidelines on diagnostic procedures from the Norwegian Breast Cancer Group.
Stimulating environment for science
CCBIO has created a stimulating science culture for young investigators and future group leaders. The CCBIO Research School for Cancer Studies (RSCS) is the first cancer-based research school in Norway and includes basic courses, junior scientist symposia (four times a year, organized by postdocs), visiting faculty and mentoring sessions. The RSCS includes CCBIOs monthly research seminars, special seminars and CCBIO’s annual symposium, the latter is now an established international meeting with well above 200 participants. Networks have been initiated, such as the Nordic Biomarker Network, originating from the First Scandinavian Pathology Symposium in Bergen 2016, focusing on advanced tissue marker studies. Importantly, CCBIO has initiated projects in ethics and economics related to biomarkers and cost-effective practice.
Two books are soon to be published:
- Lars A. Akslen & Randolph S. Watnick (Eds.) Biomarkers of the Tumor Microenvironment. Springer 2017
- Anne Blanchard & Roger Strand (Eds.) (2017): Social and economic aspects of cancer biomarkers. Bergen: Megaloceros Press 2017.
CCBIO is actively engaging with the society, through participation in public meetings, in social media, and through mass media, with stories and reports in newspapers and on prime-time television, communicating new developments in the field and commenting on research findings and oncology politics.