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CCBIO Annual Report

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CCBIO Annual Report 2021:

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

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 2021

Through 2021, we have again experienced repeated transitions between hope and disappointment - in our lives and in the way science can be done. By continuous adaptations and professional plasticity, we have learned to keep working and do our best to achieve our short-term and long-term goals. Quite unexpected, the mysterious “omics of omicron” turned out to represent some optimism more than the opposite. By the end of the year, things were slowly getting back to normal - or the “new normal”.

Our center has kept up its activity and pace as much as possible. The CCBIO Annual Symposium on May 19-20, 2021, was again organized - as a digital event this year, but with increased attendance and significant international presence and visibility. Several world-class scientists participated, such as Bernd Bodenmiller, Hans Clevers, Klaus Pantel and Morag Park. The many discussions were lively and fruitful. In particular, speed-presentations by in-house and external PhD candidates and postdocs were refreshing and most stimulating.

From the fall season, a couple of events should be mentioned. By “hybrid presentation”, Robert S. Langer, Massachusetts Institute of Technology, presented the Falch Lecture (UiB) entitled “Creating and implementing breakthrough technologies in biotechnology and nanotechnology”. Around 200 people enjoyed a truly inspirational talk from a “scientific giant”. Remembering his early mentor, the late Judah Folkman, Langer motivated the audience to pursue ideas and keep asking fundamental questions. In 2021, Bjørn Tore Gjertsen, co-director of CCBIO, received the prestigious King Olav V’s Prize for Cancer Research. In a celebration seminar organized by CCBIO, Gjertsen was praised for his tireless efforts as a translational scientist and as a devoted clinician.

We have realized the deep importance of personal proximity in science. Although hypercommunication by Zoom or other platforms might be quite efficient in some settings and for brief updates, the importance of on-site contact cannot be over-estimated. The science culture is dependent on mingling and small talk at meetings, and we therefore look forward to the upcoming 10th CCBIO Annual Symposium, to be arranged in-person on May 10-11, 2022.

CCBIO has continued to present significant findings in the biomarker field, ranging from development of new experimental models and methods, to the description of signaling pathways and spatial architecture at the single-cell level in malignant tumors. Notably, functional diagnostics represent a key development in real-time monitoring and fine-tuning as a basis for adaptive therapy and has been developed further. From our ELSA team, an important thesis was defended this year, “Precision and Uncertainty” by Eirik J. Tranvåg. Finally, several significant grants and important recruitments have been landed. 

Three CCBIO Opinion pieces are included in this report. Strell presents an update on possibilities and challenges of spatial mapping techniques. Reed gives an introduction to the important and difficult field of how to handle personal data in contemporary biomedical research and points to the necessity of international coordination. Bertolaso provides an intriguing analogy on how cancer research can be understood from a more philosophical point of view. Take your time and reflect on these comments.

At this point, we still have to modify and redefine some of our activities in science. We have experienced the perils of the pandemic, and nothing should be taken for granted – in science and in life. As we are turning another corner, we should more than ever stick to the core values of critical thinking, communication, and collaboration.

Director's comments 2020

During 2020, we all went viral and virtual. The COVID-19 pandemic became an unexpected and unprecedented challenge, and CCBIO-20 has done its best to step up and rewire a range of activities. Paradoxically, this adaptation process has presented possibilities for improvements. We have followed a very steep learning curve, both in science and society, and at many different levels. Regarding the disease itself, the need for precise biomarkers to predict aggressive conditions certainly represent a parallel to some of our challenges in the cancer field. Cost-calculations are important, and currently, compliance with guidelines is a major issue.

Our responses to the pandemic demonstrate how we can do things differently. Many of our seminars, courses and other events have become web-based, with increased attendance rates and significant international participation. In situ meetings have been replaced by in zoom interaction, and the emerging zoom fatigue has been realized. Notably, the stimulating small-talk has been difficult and limited, and “social closeness” has been reduced to a minimum.

With reduced activities in our laboratories during 2020, CCBIO has still had an active year. Among the most immediate consequences, our main gathering at Solstrand, the CCBIO Annual Symposium, had to be cancelled, and this educational and joyous networking event has been sorely missed by all of us. In the chapter on Scientific activities and progress, some of our reported results have been briefly described, on various biomarkers and how these can be applied in clinical settings. Our efforts in the field of multi-marker profiling of single cells and cell-signaling, in liquid or solid states, have continued by using our mass cytometry platform.

We are proud that two of our candidates finished their thesis work on health economics during late 2020, the first ever for CCBIO in this field. Dr. Kelly Mikyung Seo was awarded her PhD by the London School of Hygiene and Tropical Medicine for her thesis titled “Economic evaluations of companion cancer biomarkers for targeted therapies”. The thesis by Dr. Ana Beatriz Luís titled “Essays on Economic Incentives and Implications of Biomarker Tests” was accepted for defense at UIB in 2020 and successfully defended in early 2021.

Four CCBIO Opinion pieces are included in this Annual Report. Engelsen and coauthors describe the many complex challenges in todays’ precision medicine field. Despite the powerful methods of mutational profiling, only limited success can be seen in terms of treatment efficacy. The need for more functional phenotypic biomarkers and adaptive therapy is evident. Tranvåg discusses how cancer drugs are funded and prioritized. More and more costly treatments, with modest and uncertain benefits, are appraised by the drug reimbursement system, and the author argues that the system for evaluating cancer therapies has to change, for example by establishing guidelines and frameworks for socially responsible licensing, and by drug repurposing to reduce costs. In an interesting piece on breast cancer prevention, LaBarge argues that microenvironment-based drivers at the epi-genetic level are important to understand breast cancer incidence, and he discusses how the disease can possibly be prevented. A deeper understanding of the biology of aging is essential to increase our knowledge in this field. Finally, Cleuren presents some reflections on career development for young talents. How is it possible to better bridge the gap between the recruitment level and faculty positions? What are the available tools? A career plan is essential, as is active and organized CV-building and careful mentoring. For these reasons, the CCBIO Masterclass Program was launched during 2020 to promote career development.

What have we all learned this last year? The importance of adaptation and flexibility, continuous learning, and how to meet unexpected challenges, are really some of the key hallmarks of progress, for science and for the society. As these few lines are written, we face another COVID-19 wave in our country, and the problems are not over. As in science, it is important to be both realistic and optimistic, and to keep up the good work.

Lars A. Akslen, Director of CCBIO

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.)