The Department of Biomedicine

BBB seminar: Nils Halberg

Tumor ecosystems: the obesity-cancer connection

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Nils Halberg
Department of Biomedicine, University of Bergen

Heterogeneity within epithelial tumors, the most common form of cancer, is now recognized as a major cause of tumor progression. Heterogeneous malignant cells carry both the oncogenic mutations that initially prompted uncontrolled clonal growth, as well as an assortment of acquired epigenetic and transcriptional activation of stem cell features, invasiveness, survival, chemotherapeutic resistance, immune modulation and metastasis. Tumor progression can thus be seen in an evolutionary perspective, where the fittest subpopulations within the original heterogeneous tumor mass, will survive and become the primary driver of malignancy. In this regard, the fittest subpopulation is importantly also defined in its connection to the tumor microenvironment and the cellular ecosystem therein. The interplay of the tumor mutational spectrum and microenvironmental selective pressure ultimately determines outgrowth of aggressive tumor cells. We hypothesize that a key selection pressure on tumor cells is the metabolic physiology of the host. As extensive epidemiological evidence indicates that obesity is a significant driver of cancer development and spread we propose that the altered metabolic landscape of obese cancer patients enforces selection of a more aggressive cancer phenotype. By addressing this fundamental biological question we aim to uncover novel discoveries of the basic interactions between tumor cells and the host microenvironment. The mechanistic insight from these studies will also potentially form the basis for development of targeted therapeutics to treat the rapidly expanding group of obese cancer patients worldwide.

Chairperson: Rolf K. Reed, Department of Biomedicine