Professor Akslen is a specialist in surgical pathology and is directing the Tumor Biology Research Group at the Department of Clinical Medicine (University of Bergen). Since 2013, he is also the director of Centre for Cancer Biomarkers CCBIO. Akslen´s team, as is CCBIO, is engaged in translational cancer research.
About the group and its research focus
The aim has been to discover and validate novel tissue-based cancer biomarkers, for better biological understanding and improved prediction of aggressive tumor behaviour. Hopefully, such markers can assist in molecular classification and grading of malignant tumors, as a better guide for precise treatment of the patients. The group has concentrated on the tumor microenvironment.
The group´s projects
The aim of the individual studies is to provide better biological understanding and improved markers which can assist in prediction of aggressive tumor behavior and be clinically helpful. The group has concentrated on tissue-based biomarkers examined in cohorts of various human cancers (breast cancer, malignant melanoma, prostate cancer), in combination with cell and animal models to improve translation.
The team is currently targeting the following projects:
• Proteomic tissue profiling of luminal (receptor positive) and non-luminal (receptor negative) breast cancer.
• Role of Nestin as a marker of BRCA1-related, basal-like and aggressive breast cancer.
• Markers of tumor-vascular and angioimmunogenic interactions in breast cancer.
• Precision markers of tumor proliferation and invasive properties in relation to clinical applications in breast cancer.
• Role of stromal integrin alpha11 expression in breast cancer.
Important research results
• Studies have used proteomic profiling of whole tumor tissues, laser capture microdissected tissues (epithelial component, tumor stroma), whole cell lysates and secretome profiling (6 basal-like and 6 luminal-like cell lines). Data indicate significant differences of the stromal proteome across breast cancer subtypes. Disease progression might be modeled based on stromal protein profiles. Follow-up studies are ongoing.
• Expression of Nestin was found to correlate strongly with basal-like and BRCA1-associated breast cancer, and associated with stemness and angiogenic profiles. Cell studies using knock-in and knock-out strategies are ongoing.
•Data indicate that there is a difference between blood vessel and lymphatic involvement by tumor cells in high-grade breast cancer, and tumor associated macrophages (TAM) seem to be involved in this process. As a novel observation, increased microvascular proliferation was related to certain gene expression patterns and 6p21 amplification. Microvessel density predicted the response to bevacizumab in large and locally advanced breast cancers, and HSP27 associated with response to bevacizumab in metastatic melanoma.
• The team reported on tumor proliferation markers in breast cancers and how they change from primary tumors to metastases. The group found that 15% of breast cancers changed from low proliferation (primary tumors) to high in metastases. Data on extra-nodal spread of lymph node metastases and prognostic impact has been published and included as novel measures in national breast cancer guidelines by NBCG (HDir).
• Studies on the expression of alpha11 integrin in human breast cancers are ongoing in collaboration with Drs. Reed and Gullberg.
• In other projects, BRAF-V600E protein expression represented a novel progression marker in cutaneous melanoma. In a collaborative study with Dr. Watnick (Boston), the importance of prosaposin (PSAP) and thrombospondin-1 (TSP-1) for cancer progression was found.
Plans for the future
Ongoing projects will further explore the phenotypic diversity in breast cancer, with special focus on tumor-microenvironmentbased classification (vascular response, immune response, neural response) and concentrate on tissue-based proteomics profiling. Studies aim to be extended by mass cytometry (CyTOF).
Current challenges in the field
A major challenge in the field of tissue profiling is to fully account for the complexity and heterogeneity within malignant tumors. Thus, a key development will have to account for how these features shall be represented and reported, when using multiple simultaneous biomarkers (multiplex studies, mass cytometry). Ultimately, complex biomarker profiles should translate into improved biological understanding and precise diagnostics and treatment.
Spring 2016 Interview
Lars A. Akslen is an award-winning specialist in surgical pathology and has over the years initiated many research projects - with a focus on breast cancer, malignant melanoma and prostate cancer. He might study tiny biomarkers in the microscope, but the translation to new and better cancer medicine is of great importance. Akslen knows how to keep busy. He is not only the director of CCBIO, he also directs the Tumor Biology Research Group at the Department of Clinical Medicine at UIB.
What is a biomarker and how can your findings be put to use for cancer patients?
"According to the NCI definition, a biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease; a biomarker may be used to see how well the body responds to a treatment for a disease or condition. In my language, a cancer biomarker (or a biomarker signature) is the biological fingerprint or barcode of a patient´s cancer, telling us how aggressive it is, how it can be treated, and showing that each cancer is different. We are now starting to use biomarkers in molecular classification and grading of cancers, paving the way for precise therapy."
Can you tell us about your main research projects of 2015?
"We have realized that malignant tumors not only consist of tumor cells, but they are also dependent on the supporting microenvironment, such as the tumor circulation, to grow and spread. Improved markers of tumor angiogenesis have been identified, and we have discovered novel angiogenesis drivers in aggressive breast cancers. During the last years, we have also been looking at how quantification of tumor cell proliferation may assist in better classification of breast cancer."
In your work, you seem to follow the whole process from basic research to new and improved cancer therapies?
"For me, the chain-of-evidence from model studies to mapping of patient tumor tissues and detection of new targets and treatment modalities is a closed circle and an open field at the same time."
What are your goals when it comes to scientific findings?
"The ultimate goal is to discover novel and unexpected features of malignant tumors that can eventually be applied in practical medicine."
Find Akslens's PubMed publication list here.