Title
Evaluation of hair follicles as a surrogate tissue for pharmacodynamics response in xenograft tumors
Advisor(s)
Wendy Smith
Contributor(s)
Joel Klappenbach, Erin Cram
Date of Award
2012
Date Accepted
3-2012
Degree Grantor
Northeastern University
Degree Level
M.S.
Degree Name
Master of Science
Department or Academic Unit
College of Science, Department of Biology
Keywords
biology, pharmaceutical sciences, molecular biology, biomarker, hair follicle, Notch, pharmacodynamic response, pre-clinical model, surrogate tissue
Disciplines
Biology | Pharmacology | Pharmacology, Toxicology and Environmental Health
Abstract
Identification of an easily accessible and pharmacodynamically robust surrogate tissue for tumor biopsies is essential for rapid drug development in oncology. Blood–borne markers are the gold standard for monitoring pharmacodynamics for many diseases, although they are not always relevant for many cancers. Plucked hair has gained attention as a surrogate tissue as it is an epithelial tissue similar to the origin of >80% of tumors, has good drug exposure and is highly proliferative as with many tumors. We have linked the pharmacodynamic response of hair follicles and tumors in vivo using a mouse xenograft model to facilitate the development of clinical pharmacodynamic biomarkers. A Notch driven xenograft model known to respond to a gamma–secretase inhibitor was created to compare plucked hair, skin biopsies and whiskers as surrogate tissues for tumors. Hair growth synchronization was induced in mice by depilation followed by collection of tumor, hair, whiskers, skin and blood samples during each phase of the hair cycle. A qPCR assay was developed for hair phase identification using published gene expression patterns in skin biopsies as a guide. A published Notch Signature Set, in addition to a tissue responsive Signature Sets developed in this thesis, was used to determine whether hair growth phase affects pharmacodynamic readout. This information allowed creation of a preclinical model with the potential to drive quick decisions in the clinic about target modulation and treatment.
Document Type
Master's Thesis
Rights Information
copyright 2012
Rights Holder
Mary-Kamala Menon
Permanent URL
Recommended Citation
Menon, Mary-Kamala, "Evaluation of hair follicles as a surrogate tissue for pharmacodynamics response in xenograft tumors" (2012). Biology Master's Theses. Paper 17. http://hdl.handle.net/2047/d20002659
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