Primary Research Focus
The De la Puente lab is focused on the role of tumor microenvironment (TME) in cancer progression, drug resistance and cancer immunology. The TME is highly complex including stromal, immune, and endothelial cells, signaling molecules, oxygen tension, and the extracellular matrix. Classical two-dimensional (2D) cultures fail to provide an adequate model for the complexities of human tumors. Our lab is developing personalized 3D models of the tumor microenvironment in order to more accurately mimic cell-cell and cell-matrix interactions. Our lab currently focuses on developing three dimensional models of solid tumors for personalized medicine. Through these culture models, we hope to gain a deeper understanding of the role of the tumor microenvironment and their accessory cells during cancer progression, drug resistance and cancer immunology for each individual patient.
Behind the Research
The tumor microenvironment (TME) is increasingly recognized as a major regulator of carcinogenesis, a growing number of studies have focused on the TME to explore the complex mechanisms underlying disease progression and drug resistance to predict clinical outcome. In addition to neoplastic cells, the TME consists of extracellular matrix (ECM), numerous stromal cell types (fibroblasts, endothelial and immune cells) with many different cytokines, chemokines, and growth factors, which makes up to 80% of a tumor. Tumors are 3D structures by nature and these produce a gradient of both oxygen and drug concentration as a function of the distance from blood vessels; impacting the sensitivity of tumor to therapeutics. Tumor cell lines, despite their essential relevance for basic biology studies, poorly reproduce the heterogeneity of tumor tissues in vivo, thus urging the use of cells or tissue fragments derived from cancer specimens. Classic 2D culture models mainly rely on tumor cell lines and lack the ability to preserve all the cellular and non-cellular components of the TME. These cultures fail to incorporate drug and oxygen gradients, causing the cancer cells become more sensitive to therapies in vitro than the real situation in vivo and viability of primary tumor cells rapidly decreases upon 2D culture. Our lab focuses on the development of patient-derived 3D culture models allowing for the recreation of the cellular and non-cellular components of the TME, mimicking tumor hypoxia, and incorporating personalized tumor heterogeneity to provide biological insights into the role of the TME on tumor progression, drug resistance and cancer immune escape.
Elucidate the role of the tumor-stroma crosstalk in tumor progression and drug resistance
Investigate the role of TME physical features on cancer immune escape
Translational Research: Personalized medicine
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