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Journal of Oncology
Volume 2010 (2010), Article ID 396286, 13 pages
http://dx.doi.org/10.1155/2010/396286
Research Article

Architectural Heterogeneity in Tumors Caused by Differentiation Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

1Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
2Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
3Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
4Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

Received 25 December 2009; Accepted 22 January 2010

Academic Editor: Arkadiusz Dudek

Copyright © 2010 Youcef M. Rustum et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.