Centre for Cancer Biomarkers CCBIO
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CCBIO Annual Report

Read CCBIO's Annual Reports!

Front pages of all CCBIO annual reports.

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CCBIO Annual Report 2020:

Paper version as pdf. (Allow some minutes to download)

CCBIO Annual Report 2019:

Paper version as pdf. (Allow some minutes to download)

CCBIO Annual Report 2018:

Paper version as pdf. (Allow some minutes to download)

CCBIO Annual Report 2017:

Paper version as pdf. (Allow some minutes to download)

CCBIO Annual Report 2016:

Paper version as pdf. (Allow some minutes to download)

CCBIO Annual Report 2015:

Paper version as pdf.

Digital version including video.

CCBIO Annual Report 2014:

Paper version as pdf.

CCBIO Annual Report 2013:

Paper version as pdf.

Director's comments 2019

A main goal for CCBIO is to create and maintain an interactive scientific community as a stimulating soil for the many scientific ideas and talents. Multiple meetings and meeting places are important to increase collaboration and networking between senior scientists and group leaders, and among younger researchers as a resource for the future. The CCBIO Research School for Cancer Studies is instrumental to achieve this. 

Scientific communication is another cornerstone. We need to communicate our findings not only in the best scientific journals, but also to our colleagues and to the general public, among them key opinion leaders and politicians. Of particular importance is that we should increase our interaction with patients and their organizations. In the long run, this will widen our perspectives on “real life patients” and deepen our understanding of ultimate impact. On top of this, CCBIO has a communication effort aimed especially at children and youths in collaboration with the actor and cancer researcher Henriette Christie Ertsås, PhD, a CCBIO alumna. This program is funded by Vestland Fylkeskommune and CCBIO. The performances are interactive and have been a great success.

CCBIO has a focus on cellular communities and the integration of tissue landscapes and cellular location with functional properties in various “cellular niches” in primary tumors and distant tissues. The establishment of imaging mass cytometry by the Hyperion platform, pioneered by the Bodenmiller team, is clearly a step forward. This multi-dimensional tissue profiling paves the way for a systems biology interrogation using the tissue slide format. We have called this the “Hubble microscope” of contemporary tissue analysis, as the technology reminds us of the Hubble telescope used during the early days of deep space imaging.

Several events have taken place during 2019. The Iceland Research Meeting for some of our teams was memorable. We had a good mix of different people and research topics, ranging from biomedical research to societal and philosophical studies and projects on cancer communication. All participants gave short presentations, and we had keynote lectures on the “thalidomide story” in cancer treatment and on the art of “scientific saga telling” and interactive teaching. The lively discussions provided a basis for scientific eruptions.

Two members of our Scientific Advisory Board were honored this year. In October, Carl-Henrik Heldin, Chairman of the CCBIO SAB, received The Anders Jahre Senior Medical Prize at the University of Oslo, for his outstanding research about growth factors and cancer. Also in October, Bruce Zetter was appointed as an Honorary Doctor at the University of Bergen, for his ground-breaking studies in the fields of cancer angiogenesis and metastases, and for his unique teaching and mentoring. Congratulations to both!

Four CCBIO Opinion pieces are included in this Annual Report. Mills comments on some of the transformative forces in contemporary translational cancer research, paying special attention to big data analysis and artificial intelligence. Bremer & Wik argues that “perfect biomarkers” are extremely difficult to develop and that in many cases, “good enough biomarkers” could be efficient and advance precision management of many cancers, by balancing opportunities and limitations. Stenmarck & Nilsen discuss some of their findings related to how cancer challenges are communicated in the news, lacking in nuance and resulting in simplistic and faulty public understanding. Researchers must strive for both awareness and ownership of how their findings are presented in the public discourse. Cancer philosopher Bertolaso tells a tale about Cecil Rhodes and the diamond miners, as a metaphor for today’s “big data mining”, and she reminds us of the necessity of complex data integration to improve our conceptual understanding of the tumor systems.

At this point, it is not easy to measure the impact of our activities. In the meantime, we do our best to communicate interim outcomes in our fields. As a long-term strategy, we constantly feel an obligation to motivate our young recruits for a rewarding career in the “diamond mines” of cancer research.

Director's comments 2018

There are many roads to Rome, - and Rome was not built in one day. Likewise, there are many mechanisms promoting excellence in science. The definition of excellence is multi-dimensional, with both personal and institutional criteria, and not easy to agree on. At the same time, the metrics of excellence are evasive. On an individual level, elements such as novelty, creativity, quality over quantity, ambition, vision, perspective, well-organized teams and partnerships, and research integrity, among others, are needed. As indicated by Bruce Zetter, ”You have to compete with yourself and exceed the ordinary standards.” Certainly true but correspondingly difficult.

Multiple projects have been initiated and developed during CCBIO’s first 5-year period, on various solid and liquid cancers, using biomarker profiling of solid tissues and liquid samples for discovery and validation. During the second term, increased focus will be put on protein mapping and deep tissue profiling. CCBIO recently established equipment for imaging mass cytometry as the first laboratory in Scandinavia, and this move has been received with enthusiasm by our teams. It is well recognized that spatial resolution is needed to increase the precision and sensitivity of molecular tissue mapping. The issue is ”location, location, location.”

CCBIO as a research orchestra is constantly changing. Supporting the ongoing projects, a range of educational and training activities have been established. During 2018, Associate Investigator Elisabeth Wik was appointed as the new coordinator of the CCBIO Research School for Cancer Studies and immediately put her fingerprint on many initiatives. Notably, the INTPART-supported 3-week course in cancer-related vascular biology was arranged together with our partners from the Vascular Biology Program (VBP) at Boston Children’s Hospital and Harvard Medical School, directed by Marsha A. Moses. The interactive teaching in lectures and during discussion of assignments was a true inspiration, and we are very grateful to the VBP faculty for their support. The first cycle of student exchange between Bergen and Boston was completed during the summer of 2018.

As usual, several CCBIO ”opinions” have been included in this annual report. The challenge of data overload is commented on by Strand & Jonassen. They quote the philosopher Karl Popper warning that “too many dollars may chase too few ideas” and that “big  science may destroy great science, and the publication explosion may kill ideas.” Gullberg & Östman reflect on the dualism of the cancer stroma and cancer associated fibroblasts, which might have both stimulatory and inhibitory properties depending on tissues and biological context. In a piece by Bourdon & Gjertsen, a new wave of p53 biology is discussed, stimulated by the appearance of p53 isoforms and their roles in cancer progression. CCBIO PhD candidate Engen reflects on the outcome of novel targeted cancer therapies and the importance of a balanced view on the true benefits. In the final contribution by Aubert, the importance of innovation for real life impact is underscored.

The steps in the stairways to excellence need to be recognized and reflected on, and CCBIO will continue to support its many driving mechanisms. Whereas novel ideas is the real fundament, this must be combined with methodological developments involving new technology and strategies for big data processing. In the years to come, deep tissue profiling and molecular mapping of intact tissues will be an important area of interest.

Director's comments 2017

CCBIO2.0 has been approved, and we are proud to congratulate the entire CCBIO family with this achievement. It is most stimulating and motivating to move towards the second term and to fully promote our many ideas and different activities. This applies to a range of biomedical projects, from basic studies towards biomarker intense clinical trials as well as implementation and improved practice. On top of this, our activities in the field of ethics and economics, related to the principles and practices of priority setting, will be strengthened since this is a key component in contemporary precision medicine.

Studies of individual tissue biomarkers are still frequently performed, by us and others, and successful validation is more important than ever to increase the likelihood of clinical application. In breast cancer, the traditional TNM-classification of tumor stage has now been upgraded by including histological grade, expression of estrogen receptors and progesterone receptors as well as HER2 status into the novel concept of “prognostic stage groups” for clinical use. This represents a very exciting perspective for validated biomarkers.

A major challenge today is to account for tissue complexity and heterogeneity in malignant tumors, to study it without loosing the tissue coordinates, and to eventually report it with potential clinical consequences and perspectives. The prospects of high-dimensional tissue profiling, using multiplexing immuno-histochemical techniques or the powerful mass cytometry approach, combined with advanced bioinformatics and machine learning, are motivating. In the setting of biomarker programs in our clinical trials, such prospects are promising.

Many topics have received increased attention. The smartness of cancers is as fascinating as ever. During the past few years, aspects of tumor cell plasticity, including interactions with the immune and vascular systems, have started to emerge. This represents a huge potential for increased understanding of cancer strategies, but also challenges and possibilities of improved combination treatment.

During the last year, and according to a repurposing strategy, a panel of more than 600 commercially available FDA-approved drugs was screened to detect compounds with the novel features of inhibiting the Wnt-ß-catenin signaling pathway, and exciting results were  presented. The identification of nitazoxanide (NTZ) as a blocking compound is a novel mechanism. A national patient trial combining anti-Axl treatment with immunotherapy is actively recruiting patients. The dendritic cell based cryoimmunotherapy trial on prostate cancer (CryoIT) is progressing well. An interim analysis of the patients included was conducted during late 2017 with encouraging results.

In particular, ultradeep TCRsequencing indicated several prevalent new T-cell clonotypes as a reflection of new immunity. In leukemia, single cell profiling can be used to monitor CML patients treated with the kinase inhibitor nilotinib. In AML, a wide phospho-protein screen was performed, and the data support the impact of intracellular phosphosignaling pathways in reflecting differentiation stage and recurrent mutations. The identified proteins represent a possibility for further development of protein based biomarkers in leukemia.

The creation of a stimulating science culture is one of the most important goals of CCBIO. Howcan we apply the seed and soil principles in the scientific microenvironment? In an exchange between Francis Bacon and Roger Strand, the CCBIO Organon should be regarded as a colorful, energetic beehive.

Director's comments 2016

In the beginning of 2016, CCBIO was struck by the tragic loss of Professor Helga B. Salvesen, group leader and co-director of our center. During the last years, Helga established a strong and prolific research group at the Department of Clinical Science (UiB) and the Department of Gynecology and Obstetrics (Helse Bergen), with a focus on genetic and protein biomarkers in gynecologic cancers. She made important contributions in this field and received international recognition. At the same time, Helga was a dedicated scientist and mentor with high standards and a remarkable working capacity, in addition to being a warm and caring person. The CCBIO family, with all her colleagues and friends, will miss her. She leaves behind an impressive and inspiring legacy.

CCBIO is now moving steadily from the establishing phase to meet a range of challenges in the ambitious areas of precision medicine. The biomarker field is an important nexus between basic studies and the open range of diagnostic and therapeutic advancement, including initiatives by “movers and shakers” with biomedical expertise to big pharma representatives and politicians. The recent PD-L1 story is just one national example. Time will tell whether these processes can speed up and become more transparent and even more predictable and precise.

At the conclusion of 2016, CCBIO´s trajectory is very promising. Within the center, several projects are becoming more mature, with increasing international collaboration and interaction. We are actively recruiting younger faculty members to strengthen our future potential. In medical oncology, immunotherapy is moving centre stage, and we recently launched an investigator-based clinical trial of metastatic melanoma, using anti-Axl therapy (BGB324) developed by our collaborator BerGenBio, in combination with immunotherapy. The study is based on the emerging role of Axl regulation for immune evasion. This clinical trial includes an ambitious program of biomarker analyses at baseline and throughout treatment and follow-up, as well as economic profiling, thus highlighting the cost-effectiveness and societal perspectives. At present, Axl related projects range from basic discovery studies to clinical application, with extensive collaboration w ithin CCBIO. I n other areas, studies on matrix and vascular biology are going forward, as well as projects on drug repurposing. We have increased the use of mass cytometry and proteomics profiling to account for complexity in biomarker expression patterns, and liquid biomarker projects are being further developed.

We are continuously trying to enrich and reinvent our activities to create an inspiring science culture. The CCBIO Research School for Cancer Studies is an important tool, with basic courses, seminars, junior scientist symposia and our annual international symposium. As two other examples, CCBIO last year initiated a Nordic biomarker network with focus on tissue analysis, and we organized the first Nordic meeting on translational pathology. Also, we co-organized a meeting in Bergen with Oslo Cancer Cluster on the topic of drug repurposing.

Inspiration is a cornerstone in scientific work, and we try to stimulate our colleagues to widen the perspective and search for ideas and inputs across all research areas, and even outside the fields of science.

Lars A. Akslen

Director's comments 2015

During 2015, CCBIO as a research center and a newly established organization across several departments has gained significant momentum. The challenge in today’s basic and translational cancer research is huge. There are a lot of activities going on in different areas, and we have much information on how cancers develop and progress. However, there is a gap in the transfer of knowledge to practical medicine. This phase is very time-consuming, with complex regulatory mechanisms and long-lasting clinical trials of new treatments as part of today’s set-up. Biomarkers have yet to be fully included in trial design.

The development of a stimulating and encouraging scientific environment is an important pathway towards excellence. The establishment of the CCBIO Research School for Cancer Studies is crucial in this context. In 2015, a full program of integrated courses and seminars was conducted on various topics: Matrix biology; Cancer Research: Ethical,  economic and Social Aspects; Biomarkers and Tumor Biology in Clinical Practice; Methods in Cancer Biomarker Research; CCBIO Junior Scientist Symposium (JUSS); monthly research seminars with external visitors, and the CCBIO Annual Symposium. The half-day JUSS meetings are arranged four times a year, and these are organized by our postdocs. This has been a successful series with a suitable format for training of our young investigators in how to present data, discuss the findings, and chair scientific meetings.

Another important component of CCBIO is our many international collaborations and networks, allowing for scientific input in different areas and mobility of students as well as faculty. We have during 2015 continued our recruitment of international collaborators and advisors who are hired in part-time positions. In 2016, this network will be complete with 15 positions. Of further importance, CCBIO in 2015 received an INTPART grant from SIU and RCN to increase our international efforts towards education, as an integrated part of the research school.

Several promising research projects are now running in different teams, with increased collaboration and networking within CCBIO itself. A key area has been to better understand how tumor cells interact with and influence their surrounding microenvironment and the multiple facets of tumor plasticity. The enormous challenge in our field is to not only integrate the vast amount of information into a “unifying model of cancer biology”, but also to move this knowledge towards clinical practice without delay. We believe that smart use of individual or complex biomarkers is a necessary and cost-effective tool.

Scientific work is challenging, often difficult, and very time-consuming, but also a lot of fun. It is important to ask “stupid” and “out-of-the-box” questions all the time, and try to answer them. Unexpected findings should be followed up on, these might represent the most novel observations. And not the least, curiosity and excitement are two of the most striking hallmarks of excellence.

Lars A. Akslen


(See the report as attachment below.)


Director's comments 2014

Throughout 2014, CCBIO completed its first phase of recruitment, and many enthusiastic PhD students and postdoctoral fellows are in place and have initiated their work in different research groups. Basic studies are being performed, especially focusing on how tumor cells interact with the surrounding microenvironment, by epithelialmesenchymal transition, plasticity programs, angiogenesis induction and matrix dynamics, leading to the initiation of metastatic spread. Different classes of biomarkers and their clinico-pathologic correlations are being explored, such as genetic markers, gene expression mining and profiling, and tissue based protein marker studies. As an example of implementation studies, the aim of the multicenter MoMaTEC projects on integrated biomarker profiling of endometrial cancer is to perform stratified surgery based on validated biomarkers and imaging data.

One of the goals for CCBIO is to push experimental therapy and diagnostics for our patients. We are facing significant and complex challenges in how to attack metastasizing tumors. Recent papers support the positive responses to immunological checkpoint blockers, and studies with multiple indications are in preparation. CCBIO is participating in this effort by planning substudies with novel technologies like single cell analysis of immunophenotype and intracellular signaling of patient immune cells. This is performed in collaboration with the Clinical Trials Unit at Haukeland University Hospital. During 2014, CCBIO investigators have headed directly into the immunotherapy domain by teaming up with Bergen Technology Transfer Office and angel investors. The first patients will be treated using dendritic cell based therapy after cryoablation
of prostate cancer tissue in early 2015. In addition, the first AXL inhibitor, BGB324 from BerGenBio, entered a Phase I trial in Bergen, indicating a new era in biomedical research in our region, with CCBIO investigators participating. Through a five-year grant on liquid biopsies, various technologies for circulating cells and DNA will be explored in the setting of clinical trials.

During 2014, the CCBIO Research School for Cancer Studies was established, with several key courses, monthly research seminars, a junior scientist symposium (four times each year) and the CCBIO Annual Symposium as integrated parts. This program of educational and networking activities has been well received. Currently, CCBIO is now in the process of recruiting a team of international key collaborators in affiliated positions. This will be important to strengthen our research programs and excellence profile. Based on these efforts, 2015 will be an exciting year.

Lars A. Akslen


(See the report as attachment below.)

Director's comments 2013

We have had a busy start-up period at CCBIO, with important research data published in high-impact journals, and an international recruitment process. We have laid the fundament for our research school, and we’ve done multiple media appearances. 

On November 12, 2012, the Research Council of Norway officially announced that the Centre for Cancer Biomarkers CCBIO was awarded a Norwegian Centre of Excellence. This completed 19 rewarding months of prequalification proposals and applications at different levels. Nine founding teams in the field of translational cancer research, working together with three associated groups in bioinformatics, economy and ethics, were excited to receive this stimulating challenge. The centre was opened by RCN Director Arvid Hallén on May 30, 2013, during the 1st CCBIO Symposium.

The centre has a bold aim: to improve biological understanding, early diagnosis of and treatment of cancer, by using novel biomarkers. This is a major challenge in todays personalized medicine. The complexity of cancers, in space and time, is an obstacle for effective therapy, combined with the many escape mechanisms of progressing tumors. For the task to be successful, we will focus on targeted projects across model studies (Program 1), biomarker discovery and validation (Program 2), and clinical studies (Program 3).

We have established a Research School for Cancer Studies aimed for young recruits and future leaders, in addition to research seminars, annual symposia, and active international collaboration and networking. Taking advice from the CCBIO Council (local) and the CCBIO Scientific Advisory Board (Carl-Henrik Heldin, Uppsala; Ate van der Zee, Groningen; Bruce Zetter, Boston), we hope to fulfill our goals in the coming years and make a difference in the war against cancer.

Lars A. Akslen


(See the report as attachment below.)