Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity.

Currently there are no standard biomarkers of head and neck squamous cell carcinoma (HNSCC) response to therapy. This is, due to a lack of adequate predictive tumor models. To this end, we established cancer organoid lines from individual patient's tumors, and characterized their growth characteristics and response to different drug treatments with the objective of using these models for prediction of treatment response. Forty-three patients' samples were processed to establish organoids. To analyze the character of these organoids, immunohistochemistry, Western blotting, drug sensitivity assays, clonogenic survival assays, and animal experiments were performed. The HPV status and TP53 mutational status were also confirmed in these lines. HNSCC organoids were successfully established with success rate of 30.2%. Corresponding two-dimensional cell lines were established from HNSCC organoids at higher success rate (53.8%). These organoids showed similar histological features and stem cell, epithelial and mesenchymal marker expression to the original tumors, thus recapitulating many of the characteristics of the original tumor cells. The cisplatin and docetaxel IC50 were determined for HNSCC organoids and the corresponding 2D cell lines using drug sensitivity and clonogenic survival assays. Responses to drug treatment in vivo were found to be similar to the IC50 calculated from organoids by drug sensitivity assays in vitro. We established novel in vitro HNSCC cancer organoid lines retaining many properties of the original tumors from they were derived. These organoids can predict in vivo drug sensitivity and may represent useful tools to develop precision treatments for HNSCC.

Tanaka N ，Osman AA ，Takahashi Y ，Lindemann A ，Patel AA ，Zhao M ，Takahashi H ，Myers JN ... -  《-》

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy.

Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.See related commentary by Hill and D'Andrea, p. 828.This article is highlighted in the In This Issue feature, p. 813.

Driehuis E ，Kolders S ，Spelier S ，Lõhmussaar K ，Willems SM ，Devriese LA ，de Bree R ，de Ruiter EJ ，Korving J ，Begthel H ，van Es JH ，Geurts V ，He GW ，van Jaarsveld RH ，Oka R ，Muraro MJ ，Vivié J ，Zandvliet MMJM ，Hendrickx APA ，Iakobachvili N ，Sridevi P ，Kranenburg O ，van Boxtel R ，Kops GJPL ，Tuveson DA ，Peters PJ ，van Oudenaarden A ，Clevers H ... -  《-》

Ex vivo culture of head and neck cancer explants in cell sheet for testing chemotherapeutic sensitivity.

Lee J ，You JH ，Shin D ，Roh JL ... -  《-》

Differential Angiogenic Potential of 3-Dimension Spheroid of HNSCC Cells in Mouse Xenograft.

Choi SY ，Kang SH ，Oh SY ，Lee KY ，Lee HJ ，Gum S ，Kwon TG ，Kim JW ，Lee ST ，Hong YJ ，Kim DG ，Hong SH ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

High-throughput screening in colorectal cancer tissue-originated spheroids.

Patient-derived cancer organoid culture is an important live material that reflects clinical heterogeneity. However, the limited amount of organoids available for each case as well as the considerable amount of time and cost to expand in vitro makes it impractical to perform high-throughput drug screening using organoid cultures from multiple patients. Here, we report an advanced system for the high-throughput screening of 2427 drugs using the cancer tissue-originated spheroid (CTOS) method. In this system, we apply the CTOS method in an ex vivo platform from xenograft tumors, using machines to handle CTOS and reagents, and testing a CTOS reference panel of multiple CTOS lines for the hit drugs. CTOS passages in xenograft tumors resulted in minimal changes of morphological and genomic status, and xenograft tumor generation efficiently expanded the number of CTOS to evaluate multiple drugs. Our panel of colorectal cancer CTOS lines exhibited diverse sensitivities to the hit compounds, demonstrating the usefulness of this system for investigating highly heterogeneous disease.

Kondo J ，Ekawa T ，Endo H ，Yamazaki K ，Tanaka N ，Kukita Y ，Okuyama H ，Okami J ，Imamura F ，Ohue M ，Kato K ，Nomura T ，Kohara A ，Mori S ，Dan S ，Inoue M ... -  《-》