Patient-derived organoids to study and treat oral cancer

This technology describes a method to generate patient-derived oral cancer organoids, facilitating disease modeling and drug screening via a personalized medicine approach.

Unmet Need: Patient-specific modeling and therapy assessment for oral cancer in vitro

Oral squamous cell carcinoma (OSCC) remains a common disease worldwide despite advancements its diagnosis and treatment. With the majority of cases developing from oral preneoplasia (OP), timely assessment of disease susceptibility, as well as molecular subtyping, and screening for optimal patient-specific therapeutic approaches for both cases of OSCC and OP would improve overall survival rates. To date, there has been a lack of robust in vitro tools for research on disease pathology and patient-specific modeling of drug responses.

The Technology: Method to produce 3D patient-derived oral cancer organoids

This technology utilizes cells obtained from an oral, pharyngeal, or esophageal biopsy sample to generate 3D organoids within two weeks. This method allows patient-specific disease modeling of oral squamous cell carcinoma. These organoids have been used to accurately recapitulate disease characteristics such as cell heterogeneity, gene expression and drug susceptibility. Additionally, organoids generated via this approach have been implanted as patient-derived xenografts in mouse models for in vivo preclinical evaluation.

This technology has been validated using human patient-derived oral cancer samples.

Applications:

• Patient-derived organoids to model and study oral cancer in vitro
• Personalized-medicine approach to study resistance mechanisms and identify novel drug targets
• High-throughput drug screening in a patient-specific manner
• Research tool to identify disease biomarkers

Advantages:

• Rapid, high-throughput approach
• Facilitates drug-screening in a patient-specific manner
• Allows for further downstream evaluation via generation of in vivo patient-derived xenografts

Lead Inventor:

Hiroshi Nakagawa, M.D.

Patent Information:

Patent Status

Related Publications:

• Yoon AJ, Santella RM, Wang S, Kutler DI, Carvajal RD, Philipone E, Wang T, Peters SM, Stewart CR, Momen-Heravi F, Troob S, Levin M, AkhavanAghdam Z, Shackelford AJ, Canterbury CR, Shimonosono M, Hernandez BY, McDowell BD, Nakagawa H. “MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma” J Oncol. 2021 Jan 15; 2021: 8292453.

• Karakasheva TA, Kijima T, Shimonosono M, Maekawa H, Sahu V, Gabre JT, Cruz-Acuna R, Giroux V, Sangwan V, Whelan KA, Natsugoe S, Yoon AJ, Phillipone E, Klein-Szanto AJ, Ginsberg GG, Falk GW, Abrams JA, Que J, Basu D, Ferri L, Diehl JA, Bass AJ, Wang TC, Rustgi AK, Nakagawa H. “Generation and characterization of patient-derived head and neck, oral, and esophageal cancer organoids” Curr Protoc Stem Cell Biol. 2020 Jun; 53(1): e109.

• Kijima T, Nakagawa H, Shimonosono M, Chandramouleeswaran PM, Hara T, Sahu V, Kasagi Y, Kikuchi O, Tanaka K, Giroux V, Muir AB, Whelan KA, Ohashi S, Naganuma S, Klein-Szanto AJ, Shinden Y, Sasaki K, Omoto I, Kita Y, Muto M, Bass AJ, Diehl JA, Ginsberg GG, Doki Y, Mori M, Uchikado Y, Arigami T, Avadhani NG, Basu D, Rustgi AK, Natsugoe S. “Three-dimensional organoids reveal therapy resistance of esophageal and oropharyngeal squamous cell carcinoma cells” Cell Mol Gastroenterol Hepatol. 2018 Sep 14; 7(1): 73-91.

• Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. “The esophageal organoid system reveals functional interplay between notch and cytokines in reactive epithelial changes” Cell Mol Gastroenterol Hepatol. 2018 Jan 3; 5(3): 333-352.

Tech Ventures Reference:

• IR CU20232

• Licensing Contact: Joan Martinez