[Webinar] How to better optimize an oncology drug discovery program
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Authors: A Groulet-Martinec, O Duchamp, A Gonçalves, V Forestier, N Borie, S Debono, V Fert, P Genne, A Koki, N Guilbaud
IPSOGEN; Institut Paoli-Calmettes; Oncodesign
Evaluation of the response to the chemotherapeutic regimens in vivo is often global, mainly based on changes ln tumor mass rather than on molecular effects elicited by the drugs. Paclitaxel (Taxol8) ls a microtubule binding agent routinely used in breast cancer treatment in the clinic. Recently, a variety of cellular and molecular effects of paclitaxel have been described. These include Induction of cytokines, tumor suppressor genes, and activation of signal transduction pathways. The gene profiling of tumor cells exhibiting different responsiveness to anticancer drugs has been made possible by microarray technologies. Molecular analyses of the response to pharmacological treatment has been mainly explored in vitro and with the drug tested al high concentration. But these studies do not take into account the host environment in contributing to a given response, which is clearly of greater relevance to clinical settings. Host metabolism certainly influences pharmacokinetics, pharmacodynamics, molecular response, and drug efficacy.
ln the present study, we sought to examine the molecular events elicited by paclitaxel ln the MDA-MB231 human breast cancer cell line both ln vitro and in vivo using cDNA microarray technology.