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.
The focus of Akslen’s group has been to discover and validate novel tissuebased cancer biomarkers, especially related to the tumor microenvironment, for biological understanding and better prediction of aggressive tumor behavior and treatment response. As part of
precision pathology, such markers are expected to improve molecular classification and stratification of malignant tumors, and to aid precise management of the patients. The group concentrates on breast cancer proteomics (by Mass Spectrometry) and multi-marker spatial mapping of tumor landscapes (by Imaging Mass Cytometry).
1. Stromal proteomic patterns and stratification of breast cancer
2. Breast cancer hypoxia responses at the proteome level
3. Markers of cancer-neural interactions in primary and metastatic breast cancer
4. Role of nestin and stathmin in BRCA1-related and basal-like breast cancer
Proteomic profiling of laser capture micro-dissected breast cancer tissues has been performed by the group, separating cancer cells and
microenvironment compartments. Stromal protein signatures are different between hormone receptor positive (luminal-like) and hormone receptor negative (basal-like) tumors, being prognostically independent of intrinsic molecular classification, also after external validation. For the first time, we demonstrate that a stromal proteome signature is able to split the luminal A breast cancers in low-grade and highgrade categories (Finne et al., submitted). Further, stromal protein profiles have been integrated with breast cancer cell line secretome data from baseline and after hypoxic conditions, demonstrating metabolic reprogramming, especially among luminal-like tumors, indicating subtype-specific metabolic responses (Kjølle et al., in revision).
The group has studied the presence and association of neurogenesis and angiogenesis in breast cancer across subtypes, at the level of protein expression data (IHC), single-cell based spatial mapping by imaging mass cytometry (IMC), and by transcriptomics and proteomics patterns at case-level. Data indicate that neurogenesis and angiogenesis are associated features and linked to aggressive breast cancer, providing support to novel treatment possibilities (Wik et al., submitted).
Data from the group have indicated that Stathmin might be a regulator of angiogenic and immunogenic responses in the microenvironment of aggressive breast cancer (Askeland et al., Sci Rep 2020). The project has been extended by single-cell based spatial mapping of Stathmin in association with immunogenic and angiogenic cell populations, searching for tissue niches that could be Stathmin dependent and applied as biomarkers and potential targets for novel treatment (Askeland et al., in preparation). Nestin, which is associated with Stathmin in breast cancer, has been linked to aggressive phenotypes and considered to be a stemness marker, although the mechanisms for this is not clear (Krüger et al., Sci Rep 2017). The role of Nestin in breast cancer is being further explored by CRISPR-based knockdown and animal models (Ardawatia et al., in preparation).
A major challenge in the field of deep tissue profiling is to represent the complexity and heterogeneity within malignant tumors at the proteome level. Future studies need to improve information on spatial resolution. Mapping of cancer tissues with definition of functional cellular niches will increase the precision of data for prognostic and predictive purposes in current onco-medicine.
In the Akslen group, projects will continue to explore the phenotypic diversity and complexity of breast cancer subtypes, with focus on single-cell spatial mapping and niche architecture.
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.