title: High-content multiplexed tissue imaging and quantification for cancer drug discovery.
abstract: Targeting multiple hallmarks of cancer with drug combinations may provide unique opportunities for cancer therapeutics; however, phenotypic quantification is necessary to understand in vivo mechanisms of action of each drug alone or in combination. Immunohistochemistry (IHC) can quantify phenotypic changes, but traditional methods are not amenable for high-throughput drug discovery. In this article, we describe a high-content method to quantify changes in tumor angiogenesis, vascular normalization, hypoxia, tumor cell proliferation, and apoptosis using IHC. This method to quantify tumor model phenotypes can be useful for cancer drug discovery by increasing the understanding of: (i) tumor models used in efficacy studies, (ii) changes occurring during the growth of the tumor, and (iii) novel mechanisms of actions of cancer therapeutics.
authors.affiliation: Eli Lilly and Company, Department of Cancer Angiogenesis, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Beverly L
authors.initials: BL
authors.lastname: Falcon
authors.forename: Julie
authors.initials: J
authors.lastname: Stewart
authors.forename: Scharri
authors.initials: S
authors.lastname: Ezell
authors.forename: Jeff
authors.initials: J
authors.lastname: Hanson
authors.forename: John
authors.initials: J
authors.lastname: Wijsman
authors.forename: Xiang
authors.initials: X
authors.lastname: Ye
authors.forename: Eric
authors.initials: E
authors.lastname: Westin
authors.forename: Greg
authors.initials: G
authors.lastname: Donoho
authors.forename: Kelly
authors.initials: K
authors.lastname: Credille
authors.forename: Mark T
authors.initials: MT
authors.lastname: Uhlik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D007150:Immunohistochemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents