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Microtubule Stabilizing Agents and Ionizing Radiation: Multiple Exploitable Mechanisms for Combined Treatment

Rohrer Bley, Carla and Furmanova, Polina and Orlowski, Katrin and Grosse, Nicole and Broggini-Tenzer, Angela and Pruschy, Martin and Mcsheehy, Paul M.J. (2012) Microtubule Stabilizing Agents and Ionizing Radiation: Multiple Exploitable Mechanisms for Combined Treatment. European Journal of Cancer. ISSN 0959-8049

Abstract

Combined radiochemotherapy treatment modalities are in use for many indications and therefore of high interest. Even though a combined modality in clinical use is often driven by pragmatic aspects, mechanistic preclinical-based concepts of interaction are of importance in order to translate and implement an optimal combination and scheduling of two modalities into the clinics. The use of microtubule stabilizing agents is a promising strategy for anti-cancer therapy as part of combined treatment modality with ionizing radiation. Interference with microtubular integrity leads to defective mitotic spindle formation, cell cycle arrest in M-phase, and eventually to apoptosis or post-mitotic cell death. The major focus on the mechanism of interaction was primarily based on radiosensitization due to cell cycle arrest in the most radiosensitive G2/M-phase of the cell cycle. However, other mechanisms of interaction such as reoxygenation and direct as well as indirect endothelial damage have also been identified. In this review we summarize and allocate additive and synergistic effects induced by the combined treatment of clinically relevant microtubule stabilizing agents and ionizing radiation along a described radiobio-logical framework encompassing distinct mechanisms relevant for exploiting the combination of drugs and ionizing radiation.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5830

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