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Discovery of predictive biomarker candidates for intrinsic resistance to FOLFOX chemotherapy in colon cancer using a Top Down LC-MALDI approach

Florian Tobias Unger, Markus Meyer, Hartmut Juhl, Kerstin Anneliese David.

Abstract
Chemo resistance of cancer cells to chemotherapeutics is a main obstacle in chemotherapy to a successful outcome especially in first line, but also in later stages of chemotherapy. Chemotherapeutic agents are still the backbone of colorectal cancer therapy, but molecular determinants of chemoresistance are still lacking. The proteome of each cell is responsible for fundamental biological processes and also makes up the bulk of pharmaceutical targets and potential biomarkers. In this study, we used a newly developed top down LC-MALDI-MS-MS workflow to analyze the low molecular weight proteome of chemosensitive and chemoresistant cell lines in order to discover protein biomarker for intrinsic chemoresistance to FOLFOX chemotherapy in colorectal cancer. The discovery of predictive biomarkers for chemoresistance and the identification of molecular mechanisms underlying intrinsic chemoresistance could tremendously promote individualized chemotherapy.

Key words: intrinsic chemoresistance; predictive biomarker; Proteomics; FOLFOX therapy; colorectal cancer



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