Generation and Characterization of Patient‐Derived Head and Neck, Oral, and Esophageal Cancer Organoids

Karakasheva, Tatiana A.; Kijima, Takashi; Shimonosono, Masataka; Maekawa, Hirofumi; Sahu, Varun; Gabre, Joel; Cruz‐Acuña, Ricardo; Giroux, Véronique; Sangwan, Veena; Whelan, Kelly A.; Natsugoe, Shoji; Yoon, Angela J.; Philipone, Elizabeth; Klein‐Szanto, Andres J.; Ginsberg, Gregory G.; Falk, Gary W.; Abrams, Julian A.; Que, Jianwen; Basu, Devraj; Ferri, Lorenzo; Diehl, J. Alan; Bass, Adam J.; Wang, Yichen; Rustgi, Anil K.; Nakagawa, Hiroshi

doi:10.1002/cpsc.109

Cited by 68 publications

(68 citation statements)

References 42 publications

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“…Three-dimensional (3D) tumor organoid models have been consistently shown to faithfully recapitulate features of the tumor of origin in terms of cell differentiation, heterogeneity, histoarchitecture, and clinical drug response [ 29 – 32 ]. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study found that patient-derived organoids could accurately predict patient responses to therapy, with 100% sensitivity and 93% specificity [ 37 ]. While establishing patient-derived xenografts is costly and time-consuming, in vitro 3D organoids derived from primary cancers can be established rapidly, with successful passage within 10–14 days of in vitro growth and with >80% efficiency [ 29 ]. Thus far, we have cultivated patient-derived organoids from normal oral epithelium and OSCC.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

Yoon

Santella

Wang

et al. 2021

Journal of Oncology

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We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( p < 0.0005 ). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

Yoon

Santella

Wang

et al. 2021

Journal of Oncology

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“…The copyright holder for this preprint this version posted July 7, 2020. ; https://doi.org/10.1101/2020.07.03.20145854 doi: medRxiv preprint costly and time-consuming, in vitro 3D organoids derived from primary cancers can be established rapidly, with successful passage within 10-14 days of in vitro growth and with >80% efficiency [35]. Thus far, we have cultivated patient-derived organoids from normal oral epithelium and OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…The single cell suspension (4×10 5 /ml) was mixed with Matrigel (Corning, Corning, NY) and 2×10 4 cells in 50 μl of Matrigel were seeded into the 24-well plates. Organoids were grown for 10-14 days at 37°C in a humidified atmosphere of 5% CO2 as previously described [19]. Under an inverted phase-contrast microscope, growing organoids were observed and photomicrographed to determine their number and size.…”

Section: Htert Expression Analysesmentioning

confidence: 99%

“…These changes either by themselves or integrated can affect gene expression, cell cycle progression and apoptosis [17]. Importantly, Cdc42/Rac1 participates in the post-transcriptional control of telomerase activity by transcriptional upregulation of human telomerase reverse transcriptase, hTERT [18,19]. Hence PAKs-Cdc42/Rac1-hTERT pathway plays a central role in cancer recurrence and aggressiveness and are targeted by the prognostic miRNAs.…”

Section: Functional Analysis Of Prognostic Mirnasmentioning

confidence: 99%

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MicroRNA-based cancer mortality risk scoring system and hTERT expression linked with risk-adjusted treatment strategy in early-stage oral squamous cell carcinoma

Yoon

Santella

Wang

et al. 2020

Preprint

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We have developed and validated a novel microRNA (miRNA)-based prognostic model to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into early-stage by the TNM system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high and low mortality risk categories. Within the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% (p<0.001) with surgery only. A Cox proportional hazard model on time-to-death suggests a hazard ratio of 0.37 comparing surgery with neck dissection to surgery only (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only without neck dissection is the most beneficial treatment modality, as opposed to the high-risk group, in which surgery with neck dissection significantly improves 5-year survival. Regardless of treatment selected, those with risk score >1 may benefit from additional therapy to prevent cancer relapse. Based on functional analysis of the prognostic miRNAs, we identified hTERT (human telomerase reverse transcriptase) as a promising drug target to prevent cancer relapse, thereby improving cancer-free survival. We also established a functional platform for patient-derived organoid-based drug testing in an effort to link prognostic marker-based mortality risk assessment with appropriate risk-adjusted therapy to improve overall survival.

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Organoids for Cancer Research: Advances and Challenges

Xin,

Li,

Wang

et al. 2024

Advanced Biology

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As 3D culture technology advances, new avenues have opened for the development of physiological human cancer models. These preclinical models provide efficient ways to translate basic cancer research into clinical tumor therapies. Recently, cancer organoids have emerged as a model to dissect the more complex tumor microenvironment. Incorporating cancer organoids into preclinical programs have the potential to increase the success rate of oncology drug development and recapitulate the most efficacious treatment regimens for cancer patients. In this review, four main types of cancer organoids are introduced, their applications, advantages, limitations, and prospects are discussed, as well as the recent application of single‐cell RNA‐sequencing (scRNA‐seq) in exploring cancer organoids to advance this field.

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Generation and Characterization of Patient‐Derived Head and Neck, Oral, and Esophageal Cancer Organoids

Cited by 68 publications

References 42 publications

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

MicroRNA-based cancer mortality risk scoring system and hTERT expression linked with risk-adjusted treatment strategy in early-stage oral squamous cell carcinoma

Organoids for Cancer Research: Advances and Challenges

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