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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

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Title: Pyruvate dehydrogenase kinase 1 and carbonic anhydrase IX targeting in hypoxic tumors
Author: M. Kery, N. Oravcova, S. Radenkovic, F. Iuliano, J. Tomaskova, T. Golias

Abstract: Pyruvate dehydrogenase kinase 1 (PDHK1) and carbonic anhydrase IX (CAIX) are two of the most hypoxia-inducing proteins in tumors. PDHK1 is involved in glucose metabolism and CAIX in pH regulation, and both appear necessary for model tumor growth. Their hypoxia induces their expression and enzymatic activity, and high expression level in human tumors predicts poor patient outcome. This paper targets these two proteins both pharmacologically and genetically and in vitro and in vivo because they can lead to decreased cancer cell survival and significantly reduce model tumor growth. CAIX and PDHK1 are also important in cells originating from colorectal primary tumor and its metastasis, and our analysis reveals the unique relationship between these two HIF-1 target genes. Finally, PDHK1 and CAIX attributes predict that they are promising targets in the design of new, specific inhibitors which will negatively influence tumor cell proliferation and survival, increase standard treatment efficacy and avoid normal tissue toxicity.

Keywords: tumor micro-environment, hypoxia, pyruvate dehydrogenase kinase 1, carbonic anhydrase IX
Published online: 17-Oct-2018
Year: , Volume: , Issue: Page From: , Page To:

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