Hyper-Personalized Medicine Using Patient Derived Xenografts (PDXovo) for Metastatic Solid Tumors (PDXovo)

The goal is to use PDXovos, which are chick embryos cultivated in an ex ovo fashion that will act as a xenograft host, for drug paneling. Chick embryos as a PDX host model system offer multiple advantages, such as increased tumor take rates, rapid drug testing, a short evaluation timeframe, and an undeveloped adaptive immune system. Collectively, these advantages allow for implantation of tumor xenografts, subsequent growth in vivo, subsequent drug challenge, and subsequent evaluation for anti-tumor effects.

Patients with metastatic forms of solid tumors will be enrolled regardless of subtype. Metastases will be provided either via metastasectomy or needle core biopsy of metastatic deposits. Spinal and intracranial metastases will be included. Thoracentesis and paracentesis fluid samples yielding tumor tissue will also be included.

Tissue will be processed and briefly cultured in vitro. Upon authentication and expansion to a suitable number of cells, xenografts will be formed in the chick embryo pre-clinical model. After implantation (2 days later), drug treatments will be applied topically to each xenograft's surface. Drug treatments are: sunitinib, pazopanib, axitinib, temsirolimus, cabozantinib, gemcitabine (N>18/treatment group).

Evaluation of xenografts for anti-tumor effects will be performed via ultrasound imaging (changes in tumor volume and tumor vascularity) and confirmed by histology (H&E, TUNEL, CD31+ microvessel density). Treatments will be compared to vehicle control (5% DMSO in saline) treated xenografts. ANOVA (2-way, p<0.01, bon ferroni alpha corrected) analysis will be performed to identify treatments that lead to the greatest decrease in tumor volume and tumor vascularity (ultrasound imaging metrics). Agents identified will not be used to intervene in clinical care. Objective response rates with clinically chosen drug in each patient will be compared to the corresponding PDX drug panel results using kappa analysis.