幸运飞艇计划

CCBIO is now on the home stretch, and CCBIO 2.0 is rapidly听approaching. Since being established in 2013, we have had听10 years with core funding from the Research Council of听Norway to develop and nourish a Centre of Excellence听with multifaceted activities in cancer biomarker research听and contemporary precision oncology. While this first phase听has been truly rewarding for all of us, the excitement and听energy is now focused on the future. With key support from听the University of Bergen and multiple external grants, we听are entering the next phase on an optimistic note.听

Throughout 2022, CCBIO has been in continuous motion听with steady research activities and many efforts in science听communication and education through the CCBIO Research听School for Cancer Studies. We have a solid core curriculum of听12 courses relevant for researchers in biomarker studies, with听translational and clinical extensions. The CCBIO Masterclass听program, a year-long education of carefully selected top tier听candidates (8-10) for mentoring and career planning, is now听in its second cycle, and this concept has been very successful.听Another innovation in 2022 is the CCBIO-ARC, or Advanced听Research Colloquium, which is aimed to represent 鈥渇ood for听thought鈥� by monthly discussions within the PI-group of new听concepts and key papers in biomedical research.

We are very thankful for the efforts of our International听Faculty over the years, for their presence, advice, and听collaborative input. CCBIO would not have been the same听without the 鈥渆xtended family鈥� of all these friends. We also听thank our guests for the monthly research seminars, special听seminars and courses during 2022 and in the past. During the听10th CCBIO Annual Symposium in May, where we experienced听a strong 鈥済et back鈥� moment after the pandemic, we all felt the听importance of coming together to enjoy each other鈥檚 company听and the fun of science. We had many strong presentations,听and we will always remember and remain motivated by听Bob Langer鈥檚 fantastic journey in science and innovation.

Many important research papers have been published from听CCBIO during the last year and are commented on elsewhere听in this report. One of the latest highlights, presented in the听2022-2023 transition, is the recent work by Tislevoll et al.听(Gjertsen group) published in Nature Communications.听This elegant report demonstrates how single-cell signaling听analytics by mass cytometry can allow for very early response听prediction, eventually followed by treatment modification, in听patients with acute myeloid leukemia. Importantly, the paper听shows the significance of real-time functional diagnostics and听adaptive therapy, a model that will now be pursued even for听solid cancers. The related technique of single-cell studies by听imaging mass cytometry (IMC), established by CCBIO and听now used by many groups, is particularly promising for highresolution biomarker mapping in tumor tissues. These mass听cytometry approaches have been a strong strategic focus of听CCBIO during the last 5 years.

Two books were published by CCBIO during 2022: Anne听Blanchard and Roger Strand (eds): Precision Oncology and听Cancer Biomarkers: Issues at Stake and Matters of Concern听(Springer 2022), and Lars A. Akslen and Randolph S. Watnick听(eds): Biomarkers of the Tumor Microenvironment (Springer听2022, 2. Ed.). Thank you to all contributors 鈥� many of them听from CCBIO groups and networks.

One of the hallmarks of CCBIO has been to include studies听on societal perspectives, with projects on ethical and听economic topics 鈥� how to prioritize in a fair way, and how听to understand our many efforts in a philosophical context.听While we are focused on our individual projects and findings听from day to day, we clearly need to widen our perspectives听to see the 鈥渂igger picture鈥� and reflect on the responsibility听and long-term impact of what we do. To this effect, we have听initiated a synthesis work on our outputs and outcome that听can be observed over the years. This review will appear in听a more detailed and mature form in our final report to be听issued in 2024.

In this transitional period, we would like to quote Winston听Churchill from 1942: Now this is not the end. It is not even the听beginning of the end. But it is, perhaps, the end of the beginning.听Said in a very different context, he also pointed out another听deep truth that can be mentioned and remembered: Success听is not final, failure is not fatal, it is the courage to continue that听counts. To all the staff of CCBIO 鈥� thank you for all your hard听work and for your courage and persistence. Let us keep up听the pace and increase the momentum 鈥� together.

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

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

From the fall season, a couple of events should听be mentioned. By 鈥渉ybrid presentation鈥�, Robert听S. Langer, Massachusetts Institute of Technology,听presented the Falch Lecture (幸运飞艇计划) entitled 鈥淐reating听and implementing breakthrough technologies听in biotechnology and nanotechnology鈥�. Around听200 people enjoyed a truly inspirational talk听from a 鈥渟cientific giant鈥�. Remembering his early听mentor, the late Judah Folkman, Langer motivated听the audience to pursue ideas and keep asking听fundamental questions. In 2021, Bj酶rn Tore Gjertsen,听co-director of CCBIO, received the prestigious King听Olav V鈥檚 Prize for Cancer Research. In a celebration听seminar organized by CCBIO, Gjertsen was praised听for his tireless efforts as a translational scientist and听as a devoted clinician.

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

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

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

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

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 鈥渟ocial closeness鈥� 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 鈥淓conomic evaluations of companion cancer biomarkers for targeted therapies鈥�. The thesis by Dr. Ana Beatriz Lu铆s titled 鈥淓ssays on Economic Incentives and Implications of Biomarker Tests鈥� 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鈥� 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. Tranv氓g 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

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

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

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

Several events have taken place during 2019.听The Iceland Research Meeting for some of our听teams was memorable. We had a good mix of听different people and research topics, ranging from听biomedical research to societal and philosophical听studies and projects on cancer communication.听All participants gave short presentations, and听we had keynote lectures on the 鈥渢halidomide听story鈥� in cancer treatment and on the art of听鈥渟cientific saga telling鈥� and interactive teaching.听The lively discussions provided a basis for 蝉肠颈别苍迟颈蹿颈肠听别谤耻辫迟颈辞苍蝉.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 (幸运飞艇计划) 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 鈥渕overs and shakers鈥� 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麓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

During 2015, CCBIO as a research center and a newly established organization across several departments has gained significant momentum. The challenge in today鈥檚 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鈥檚 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, 听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听the vast amount of information into a 鈥渦nifying model of cancer biology鈥�, 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 鈥渟tupid鈥� and 鈥渙ut-of-the-box鈥� 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

听

(See the report as attachment below.)

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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

听

(See the report as attachment below.)

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 Hall茅n 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

听

(See the report as attachment below.)