MiTuMi · Bioengineered Matrices Mimicking the Lung Tumor Microenvironment

Lung cancer is the leading cause of cancer-related mortality in the world. It most often gets diagnosed at an advanced stage with a 5-year survival rate as low as 5%. Despite recent advances in development of therapeutics, lack of a comprehensive understanding of the complexity and dynamicity of the tumor microenvironment hinders effective clinical outcome. Tumor microenvironment plays a crucial role in tumorigenesis and subsequent disease progression leading to metastasis as well as resistance to therapeutics. Conventional monolayer culturing of tumor cells fails to recapitulate the essential microenvironmental aspects of native tumors whereas mouse models suffer from limited relevance, high cost and low throughput. A three-dimensional (3D) human in vitro tumor model that faithfully mimics the tumor microenvironment is key to advance the current understanding of biological processes and signaling pathways that govern these complex pathological events. I propose a biomimetic human lung tumor model that allows independent tunability and control of aberrant biochemical and mechanical aspects of the tumor microenvironment to study cellular events that govern tumorigenesis (Objective1), metastasis and drug resistance (Objective2) and patient heterogeneity (Objective3). Following a highly interdisciplinary approach where tissue engineering, material science, medicine and molecular biology converges, the implications of a tunable and biomimetic 3D human tumor model is substantial for the future of precision-medicine and development of patient- specific therapeutic regimens.