Head and neck squamous cell cancer (HNSCC) is a devastating disease. Current cell line-based models lack predictive value and are increasingly recognized as artificial and biased. Direct tumor xenografting is a strategy that has proven very powerful for disease characterization, therapy testing, and biomarker development. Tumors retain the most relevant features from the original cancers (morphologic, genetic, and proteomic), are genetically stable through multiple passages, and are predictive of drug sensitivity in the patient. The overall goal of this proposal is to develop a preclinical platform of freshly implanted HNSCC that will allow learning more about this disease and finding better and more individualized treatments. The principal investigator of this protocol has successfully accomplished this in other cancers (such as pancreatic and squamous skin cancer). Subjects undergoing routine surgery for HNSCC will be asked to consent in an IRB- approved clinical trial to donate excess, non-diagnostic tumor samples that will be implanted into nude mice in an ACUC-approved animal protocol. The tumors will be maintained alive on mice to conduct biological analyses. These will aim at establishing the optimal implantation site to faithfully maintain the features in the originator tumor, including the capability to develop metastasis. For each case we will test a heterotopic and an orthotopic implantation site, and by comparing each of the sites to the patient's tumor we will determine which is more similar using genetic drift and metastasizing capability as the endpoints. Genetic drift will be assessed by global gene expression, metastatic spread will be evaluated by micro-PET-CT and necropsy. Overall, from these studies we hope to develop a platform as close to the clinic as possible, that will enable future drug development and biomarker discovery.
The goal of this study is to develop a preclinical platform of head and neck squamous cell cancer (HNSCC), that will allow learning more about this disease and finding better and more individualized treatments. We will implant excess tumor tissue surgically removed from patients in mice. The principal investigator of this protocol has successfully accomplished this in other cancers. We implant tumors in mice because out of a very small amount of tissue we can generate a greater amount, that allows complex testing not possible in the small, original human sample. The characteristics of these tumors will be studied, and we will learn which is the best way to maintain the patient's tumor characteristics in the mice tumors.
|Keysar, Stephen B; Eagles, Justin R; Miller, Bettina et al. (2018) Salivary Gland Cancer Patient-Derived Xenografts Enable Characterization of Cancer Stem Cells and New Gene Events Associated with Tumor Progression. Clin Cancer Res 24:2935-2943|
|Manuel, Christopher A; Pugazhenthi, Umarani; Spiegel, Shannon P et al. (2017) Detection and Elimination ofCorynebacterium bovisfrom Barrier Rooms by Using an Environmental Sampling Surveillance Program. J Am Assoc Lab Anim Sci 56:202-209|
|Manuel, Christopher A; Bagby, Stacey M; Reisinger, Julie A et al. (2017) Procedure for Horizontal Transfer of Patient-Derived Xenograft Tumors to EliminateCorynebacterium bovis. J Am Assoc Lab Anim Sci 56:166-172|
|Bowles, Daniel W; Keysar, Stephen B; Eagles, Justin R et al. (2016) A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol 53:74-9|
|Morton, J J; Bird, G; Keysar, S B et al. (2016) XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene 35:290-300|
|Morton, J Jason; Bird, Gregory; Refaeli, Yosef et al. (2016) Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap. Cancer Res 76:6153-6158|
|Gan, Gregory N; Altunbas, Cem; Morton, John J et al. (2016) Radiation dose uncertainty and correction for a mouse orthotopic and xenograft irradiation model. Int J Radiat Biol 92:50-6|
|Göke, Friederike; Franzen, Alina; Hinz, Trista K et al. (2015) FGFR1 Expression Levels Predict BGJ398 Sensitivity of FGFR1-Dependent Head and Neck Squamous Cell Cancers. Clin Cancer Res 21:4356-64|
|Le, Phuong N; McDermott, Jessica D; Jimeno, Antonio (2015) Targeting the Wnt pathway in human cancers: therapeutic targeting with a focus on OMP-54F28. Pharmacol Ther 146:1-11|
|Gan, Gregory N; Eagles, Justin; Keysar, Stephen B et al. (2014) Hedgehog signaling drives radioresistance and stroma-driven tumor repopulation in head and neck squamous cancers. Cancer Res 74:7024-36|
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