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 the group has been to discover and validate novel tissue-based cancer biomarkers, especially of the tumor microenvironment, for better biological understanding and improved prediction of aggressive tumor behavior. Importantly, such markers can assist in molecular classification and grading of malignant tumors, as a better guide for precise management of the patients.
The group has concentrated on the mapping of protein patterns by using tissue compartment specific proteomics analyses (Mass Spectrometry) and imaging mass cytometry (CYTOF)
1. Proteomics portraits of breast cancer subtypes stratified by tumor cell and microenvironment compartments
2. Markers of neuro-angiogenic phenotypes in breast cancer and associations with immune responses and molecular phenotypes
3. Role of nestin and stathmin as markers of BRCA1-related, basal-like and aggressive breast cancer
Proteomic profiling of laser captured microdissected breast cancer tissues has been performed, separating the cancer cell and microenvironment compartments, and results have been compared with findings from bulk tissue analysis. Stromal protein signatures are significantly different between hormone receptor positive (luminallike) and hormone receptor negative (basal-like) tumors, being prognostically independent of intrinsic molecular classification, after external validation. Studies of cell lines (whole cell lysates and secretomes) have indicated marked differences between subtypes (luminallike and basal-like), both baseline and after exposure to hypoxia, indicating subtype-specific metabolic responses and reprogramming, and differential activation of tumor-based stimulation of the microenvironment, such as angiogenesis.
Transcriptomics data, supplemented by protein expression information and cell line studies, indicate that angiogenic, immunogenic, and neurogenic responses appear to be coordinated and different between breast cancer subtypes. These phenotypes also differ according to basic clinicopathologic characteristics and disease progression and might provide novel biomarkers and targets for more precise patient management.
Expression status of nestin (mRNA and protein), a candidate biomarker for aggressive breast cancer, was found to correlate strongly with basal-like and BRCA1-associated tumors, and also associated with stemness and angiogenic profiles. After CRISPR-based knockdown of nestin in aggressive breast cancer cells, marked changes in proteomic profiles have been observed, and animal experiments are ongoing to characterize tumor growth and metastatic spread in vivo. Further, data have shown that stathmin expression is a marker associated with nestin, and also related to angiogenic and immunogenic responses in aggressive breast cancer.
A major challenge in the field of tissue profiling is to account fully for the complexity and heterogeneity within malignant tumors. Future in situ studies need to improve information on spatial resolution of molecular data, using different endpoints such as targeted cancer diagnostics, prognostic profiles, and in particular predictive signals as integrated parts of precision oncomedicine. Ultimately, complex biomarker profiles should translate into improved biological understanding and better diagnostics and treatment.
In the Akslen group, projects will further explore the phenotypic diversity in breast cancer, with special focus on tumor-microenvironment characteristics and functional interactions. Cancer tissues and cell line proteomics will be complemented by advanced profiling using the recently established imaging mass cytometry (IMC) platform at CCBIO
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.
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.