Abstract 619: Personalized models to guide precision medicine
Authors: Pauli Chantal , Puca Loredana , Emerling Brooke M. , Hopkins Benjamin , Sboner Andrea , Elemento Olivier , Mosquera Juan Miguel , Beltran Himisha , Rubin Mark A. 
Published: July 2016

BACKGROUND

Precision oncology is a clinical approach aimed towards tailoring treatment strategies for patients based on the genetic profile of each patient's cancer. Available cell line models alone often do not accurately recapitulate the genetic profile of individual patient tumors and therefore limit preclinical evaluation of newly targeted agents. Furthermore, a high failure rate of drug candidates can be attributed in part to the use of monolayer cultures as the initial screening method that is associated with highly variable responses and does not predict clinically observed chemoresistance. In our Englander Institute for Precision Medicine we developed a program utilizing patient derived tumor organoids, in combination with individualized genomic sequencing, targeted and/or high throughput drug screenings to nominate drug candidates in a precision patient care setting. Drug candidates are further validated with personalized in vivo models. Utilizing these various genomic and biological platforms for pharmacological screenings, we can more closely recapitulate the in vivo tumor of individual patients and can more accurately model personalized therapeutic response and resistance in vitro and in vivo.

DESIGN

Fresh tissue samples were collected, washed and mechanically or enzymatically dissociated and then plated in a Matrigel (BD) scaffold with primary culture media. Primary spheres were characterized according to our cytology, histology and genomic platforms. Established and characterized tumor organoids were expanded, cryopreserved for banking, used for in vitro studies and implanted in nude mice for patient derived xenografts (PDXs) to further validate potential drug candidates.

RESULTS

Our success rate in generating patient derived pan-cancer tumor organoids is 30%, depending on specimen quality and tumor type (e.g. endometrial cancer 70%, metastatic prostate cancer 15%). Morphology and molecular profiles show good concordance among tumor organoids and native tumor tissues. The success rate in establishing PDXs from organoid cultures is currently at 70-80%. In vitro and in vivo drug screenings show tumor specific drug sensitivity.

CONCLUSION

We have developed protocols for the generation and characterization of individual patient-derived tumor organoids. Cytopathology, histopathology and molecular pathology represent important platforms in our Precisicon Medicine Program. Tumor organoid characterization, pharmacological screenings and drug validation in PDX models are effective models which can be used to tailor standard of care treatment, study drug resistance, and nominate novel therapeutic targets unique to the individual genomic landscape and biology of each tumor.

Citation Format: Chantal Pauli, Loredana Puca, Brooke M. Emerling, Benjamin Hopkins, Andrea Sboner, Olivier Elemento, Juan Miguel Mosquera, Himisha Beltran, Mark A. Rubin. Personalized models to guide precision medicine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 619.