ABSTRACT
Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.
Subject(s)
Neoplasms , Xenograft Model Antitumor Assays , Humans , Animals , Neoplasms/pathology , Neoplasms/drug therapy , National Cancer Institute (U.S.) , United States , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , ConsensusABSTRACT
Targeted disruption of the different ER genes has generated experimental animal models that are very useful in evaluating the distinct and cooperative roles of the two estrogen receptors, ERalpha and ERbeta, in reproductive but also non-reproductive tissues of both sexes. Phenotypic analysis has provided definitive experimental findings for estrogen receptor mediated physiological actions, involving ERalpha in uterine, mammary gland and neuroendocrine sites. ERbeta is involved most dramatically in the ovary as is ERalpha. More detailed studies in combination with tissue specific or inducible ER knock outs will be important for future research.
Subject(s)
Receptors, Estrogen/physiology , Animals , Female , Infertility, Male/genetics , Infertility, Male/metabolism , Male , Mammary Glands, Animal/metabolism , Models, Animal , Ovary/metabolism , Phenotype , Reproduction/genetics , Uterus/metabolismABSTRACT
Tremendous progress has been made in elucidating numerous critical aspects of estrogen signaling. New tools and techniques have enabled detailed molecular analysis of components that direct estrogen responses. At the other end of the spectrum, generation of a multiplicity of transgenic animals has allowed analysis of the physiological roles of the estrogen-signaling components in biologically relevant models. Here, we review the ever-increasing body of knowledge in the field of estrogen biology, especially as applied to the female reproductive processes.