Title: Multiscale Modeling of Novel Anti-cancer Therapies Targeting Cancer Stem Cells
Abstract: Increased understanding of the molecular drivers of tumor initiation and progression has led to targeted manipulation of intracellular signaling pathways for therapeutic benefit. For example, self-renewal and survival of cancer stem cells is highly influenced by tumor microenvironmental factors and molecular signaling initiated by cytokines and growth factors. Targeting key molecular regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising conceptual strategy for cancer treatment, yet therapies specifically directed against cancer stem cells remain scare. In this talk, a multiscale modeling framework is outlined for linking:
- (i) intracellular signaling pathways critical to cancer stem cell self-renewal and survival;
- (ii) receptor-ligand binding on the cell surface that triggers these intracellular signaling cascades; and
- (iii) population-level tumor growth dynamics and response to treatments targeting these critical molecular pathways.
Integration of these tiers of information is precisely the level of detail required to uncover possible hidden mechanisms that mediate both expected and potentially counterintuitive therapeutic effects of novel, targeted therapeutics on the cell types responsible for tumor progression. Our results suggest that nonintuitive dose scheduling strategies will optimize synergy of combination therapy.