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, and now CCBIO, are engaged in translational cancer research.
About the group and its research focus
The Tumor Biology Research Group was established in 1995 at The Gade Institute, later the Department of Clinical Medicine, (UIB). The main purpose has been to explore and validate novel biomarkers for more biologically based classification and grading of cancers, as a better guide for precise treatment. The group has focused on tumor-vascular interactions and how to determine tumor proliferation for clinical applications.
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 profiling and tissue deconvolution of luminal (receptor positive) and non-luminal (receptor negative) breast cancer
• Expression of Nestin (NES) as a marker of BRCA1-related, basal-like and aggressive breast cancer
• Precision markers of tumor proliferation and clinical applications in breast cancer
•Biomarkers of stromal characteristics and tumor-vascular interactions in aggressive cancers
The team reported that increased microvascular proliferation was associated with certain gene expression patterns and 6p21 amplification (Stefansson, et al.). Data indicated that there is a difference in blood vessel and lymphatic tumor invasion across subtypes of breast cancer (Klingen, 2016). Findings indicate that tumor proliferation in metastases might be important to predict tumor behaviour (Aziz, 2016). This is relevant for treatment guidelines. Importantly, 15% of the cases changed from low (primary tumors) to high proliferation (metastases), but treatment consequences are currently not clear. Further, a paper on improved definitions of extra-nodal growth in lymph node metastases of breast cancer has led to new national guidelines (Aziz, et al.).
In melanoma studies, and for the first time, a tissue-based biomarker (HSP27) significantly predicted the response to bevacizumab treatment of metastatic disease (Schuster, 2016). BRAF-V600E protein expression was found to represent a novel marker of melanoma progression, better than mutation status (Hugdahl, 2016). In a collaborative study with Dr. Watnick (Boston), the importance of prosaposin (PSAP) and thrombospondin-1 (TSP-1) expression for ovarian cancer progression was reported (Wang, 2016), expanding on previous findings from this collaboration.
Plans for the future
The team will continue to combine studies of tumor tissue from patients (primary and metastatic), with experimental cell and animal models. In particular, the following areas will be concentrated on: Proteomic profiling and tissue deconvolution of luminal (receptor positive) and nonluminal (receptor negative) breast cancer. Human breast cancers (matched luminal and non-luminal cases) are studied in parallel with hormone receptor positive and negative cell lines. Networks reflecting tumor-stroma signalling are being focused in this search for novel biomarkers and targets (Birkeland, 2016). A novel tool for in silico tissue deconvolution has been developed (Dimitrakopoulou, et al.). Expression of Nestin (NES) as a marker of BRCA1-related, basal-like and aggressive breast cancer. The team is working on NES-based algorithms for BRCA1-prediction, and for improved delineation of basal-like tumors. NES expression is associated with stemcell phenotypes (Kruger, et al.).
Biomarkers of tumor stromal characteristics and vascular interactions in aggressive cancers. In a collaboration with Oslo University Hospital, the team is exploring the value of angiogenesis markers in predicting the response of locally advanced breast cancer to bevacizumab anti-angiogenesis treatment (Kruger, et al.). The predictive value of stroma-related serum markers is explored in trials of metastatic melanoma and renal cancer.
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.