Centre for Cancer Biomarkers (CCBIO)

CCBIO's vision is to discover, validate and apply biomarkers to improve the understanding of cancer biology, increase diagnostic precision, and improve targeted treatment in a cost-effective and socially responsible way. CCBIO has a two-armed pipeline of biomedical and societal studies. The center explores the concept that cancer development and progression can be understood not just in terms of intrinsic changes in tumor cells, but also by their interaction with the tumor microenvironment (TME) in complex tissue niches locally and systemically. The main aims are to characterize biological and molecular mechanisms of tumor-stroma interactions, and to discover and confirm new diagnostic biomarkers and therapeutic targets for clinical testing and implementation. CCBIO utilizes preclinical models (cell lines, organoids, PDX, imaging) and tissue samples from human cancer cohorts. Novel cutting-edge technology has been established (e.g. imaging mass cytometry, single-cell mapping). The center has spearheaded economic evaluation and ethical studies of biomarkers (ELSA/RRI), aiming to examine new biomarkers in a societal perspective, investigating priorities and how new markers and treatments influence costs and benefits, and to promote sustainable cancer research. Projects are performed in a context of strong educational programs provided by Norways only research school for cancer studies with national and international participants. Since 2022, two cycles of the CCBIO-Masterclass mentoring program has been completed. Scientific results are communicated to professional and lay audiences including a program for school children. CCBIO has uncovered novel biological properties of the cancer organism by which tumor cells can interact with the surrounding TME to support their growth and spread, and how to monitor such processes locally and systemically. Related molecular biomarkers have been translated to improve precision diagnostics and therapy for cancer patients. During 2013-2023, data on how tumor cells influence local and distant TME tissues have been reported, including the balance between immune stimulation and immune suppression (Sui et al., Nat Commun 2022). Proteins like Axl, Prosaposin, Stathmin and P53 are important regulators of the TME and tumor progress in different cancer types, and Nestin, a regulator of cellular plasticity and stemness, has been linked to aggressive breast cancer. Technologies such as Imaging Mass Cytometry with single-cell mapping and spatial analysis have been established to advance deeper studies of cancer tissues (Lien et al., EBioMedicine 2022). Proteomics analysis of TME tissues indicate unique stromal programs as features of cancer progression, including hypoxia induced metabolic switches (Kjølle et al., Nat Commun 2023). Biomarker-intense clinical trials on cancer immunotherapy are being conducted. Receptor sequencing of T-lymphocytes have demonstrated marked diversity of the immune response following treatment. Anti-Axl therapy by bemcentinib has been implemented in multiple trials with companion biomarker studies (Li et al., Cell Rep Med 2022). Drugs such as nitazoxanide was reported, potentially representing new cancer therapy by drug repurposing. In liquid cancers, functional assays by single-cell profiling have been developed as a basis for early-phase dynamic monitoring and adaptive treatment (Tislevoll et al., Nat Commun 2023). CCBIO has strong internal and international collaboration, also by recruitment of 14 international top scientists to adjunct positions. The center has organized 10 international symposia and multiple larger meetings and workshops, e.g. symposia on P53 (2017), Liquid Biopsies (2018), and Deep Tissue Profiling (2019). In 2016, CCBIO initiated the annual Scandinavian network symposium for tissue-based tumor studies (SCANPATH). CCBIO builds long term competences, e.g. through the open CCBIO Research School for Cancer Studies with 12 key courses, monthly seminars with international speakers, and the CCBIO Junior Scientist Symposium organized by postdocs and PhD students 4 times annually. CCBIO’s INTPART program was funded for a second phase (NFR 2020), in collaboration with the Vascular Biology Program at Boston Childrens Hospital and Harvard. Significant external funding was achieved during 2021-2023, including a Trond Mohn Foundation (TMS) Starting Grant to Dr. Carina Strell, Uppsala University, on early breast cancer. Recently, one of CCBIO’s investigators (Ole Frithjof Norheim) received CoE-funding. Two CCBIO-based books were published in 2022: Bremer & Strand, eds: Precision Oncology and Cancer Biomarkers: Issues at Stake and Matters of Concern. (Springer, 2022); Akslen & Watnick, eds. Biomarkers of the Tumor Microenvironment. (Springer, 2022; textbook, 2. ed.).

English version The vision of the Centre for Cancer Biomarkers is to discover, validate and translate functional cancer biomarkers to improve biological understanding, diagnosis and treatment of aggressive cancer. The Centre builds on the novel concept of a "contextual cancer code" where tumor cells are educated by the microenvironment to behave aggressively. Understanding the complex cancer tissue landscape requires new approaches that capture the influence of tumor stroma and move beyond the linear focu s on genetic alterations. The Centre aims to develop current knowledge and competence in this novel field by: 1) characterizing biological and molecular mechanisms in tumor-stroma interactions, and 2) identifying and validating new diagnostic markers and therapeutic targets for rapid clinical implementation (such as Axl, Stathmin, Prosaposin). The vision will be fulfilled through three integrated and overlapping research programs, each with complementary projects: 1. Mechanisms of tumor-microenvironment interactions (preclinical models); 2. Identification and validation of prognostic and predictive biomarkers; 3. Clinical implementation of biomarkers and targets (clinical studies and trials). The CCBIO will rely on innovative preclinical models comprising multiple cell types and matrix components, and novel interrogation methods for measuring underlying molecular mechanisms of tumor-stroma interactions. Further, the Centre will use large biobanks and collections of specimens and clinical information ( in-house and through collaboration), and a Clinical Trials Unit. The Centre model will promote rapid clinical translation of basic studies through long-term competence building, researcher training facilitated by strong collaboration networks, investigator mobility and collaboration with industry partners. This approach aims to provide an extended "molecular taxonomy of cancer" beyond standard schemes, to enable a "molecular forecast" of cancer prognosis and response to treatment. Norwegian version Centre for Cancer Biomarkers visjon er å finne, validere og anvende gode biomarkører for kreft. Dette vil forbedre vår forståelse av sykdommens biologi, og dermed øke presisjonen i diagnostisk utredning og bedre effekten av målrettet behandling av ulike kreft former. Senteret bygger på det nye konseptet om en kontekstuell kreft-kode, dette at kreftsykdommers utvikling og progresjon må forståes ikke bare utifra endringer i selve kreftcellene, men også deres interaksjon med mikromiljøet i svulstene. Det å fors tå det komplekse vevslandskapet i svulster krever nye tilnærminger som inkluderer bedret forståelse av tumors støttevev. Senteret sikter mot å utvikle kunnskap og kompetanse innen dette nye feltet ved å: 1) karakterisere biologiske og molekylære mekanisme r for tumor-stroma og tumor-vaskulær interaksjon, og 2) identifisere og validere nye diagnostiske markører og terapeutiske mål for rask klinisk anvendelse (eksempelvis Axl, Stathmin, Prosaposin). I tillegg til biologisk rettet forskning vil senteret etablere prosjekter innen etikk og helseøkonomi, for å undersøke hvordan bruken av nye kreftmarkører virker i et samfunnsperspektiv. Visjonen vil bli oppfylt gjennom tre integrerte forskningsprogrammer, hvert av disse med prosjekter som utfyller hverandre: 1. Mekanismer for interaksjon mellom tumorceller og mikromiljø (prekliniske modeller), 2. Identifisering og validering av prognostiske og prediktive biomarkører, 3: Klinisk anvendelse av biomarkører og nye behandlingsmål (kliniske studier og utprøvende diagnostikk og behandling). Senteret vil basere seg på innovative prekliniske modeller som inkluderer et bredt spekter av celletyper og matrixkomponenter (in vitro) og ulike dyremodeller med avansert bildeanalyse (in vivo). Senteret vil anvende store biobanker og databanker med klinisk informasjon (lokalt og gjennom vitenskapelig samarbeid). Senterets organisering vil søke å fremme rask klinisk anvendelse av resultatene. I tillegg vil senteret bidra til mer langsiktig kompetansebygging, forskerutdanning tilre ttelagt gjennom sterke samarbeidsnettverk nasjonalt og internasjonalt med god forskermobilitet, og samarbeid med industrielle partnere. God formidling av senterets aktivitet og resultater blir en viktig oppgave. Senterets tilnærming tar sikte på å forbedre molekylær klassifisering av kreftsvulster for å forbedre diagnostikk og skreddersydd behandling.