Tumor organoids: applications in cancer modeling and potentials in precision medicine

Xu, Hanxiao; Jiao, Dechao; Liu, Aiguo; Wu, Kongming

doi:10.1186/s13045-022-01278-4

Cited by 105 publications

(62 citation statements)

References 204 publications

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“…Individualized chemotherapy may help patients receive appropriate chemotherapy drugs, improve the pertinence of treatment and prolong the overall survival to the greatest extent. In recent years, with the development and maturation of tumor organoid models for screening and selecting appropriate chemotherapy drugs, individualized chemotherapy has become a reasonable choice to improve efficacy and reduce ineffective treatments (16,(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Establishment of gastric cancer organoid and its application in individualized therapy

et al. 2022

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The application of cancer organoids is of great value in individualized therapy as an embodiment of the tumor of a patient, a gastric cancer organoid model was established and its application in individualized drug screening was explored. The primary tumor tissues of 3 patients with gastric cancer who underwent primary surgery at the Fourth Department of General Surgery of the First Hospital of Lanzhou University (Lanzhou, China) between July and August 2021 were selected and digested with mixed enzymes to prepare cell suspensions. Of these, two were cultured by mixing with Matrigel, while the cells from the third patient were placed in a 24-well ultra-low adhesion plate for suspension organoid culture. After intensive organoid growth, they were digested, passaged, cryopreserved and thawed for further analyses. The formation of gastric cancer organoids was observed under an inverted microscope. One case was selected, and organoids were compared with the original tumor tissue via H&E and immunohistochemical staining to evaluate the consistency of the two. Finally, paclitaxel, oxaliplatin and fluorouracil were administered to the organoids to verify the value of screening individualized drugs. It was indicated that the passage and cryopreservation of gastric cancer organoids were successfully established in all three cases. The H&E and immunohistochemical staining results suggested that the structure and protein expression of the organoids were highly similar to those of the source tumor tissue. The use of established gastric cancer organoids for individualized chemotherapy drug screening is of high clinical value. Gastric cancer organoids with high similarity to the original tissue may be successfully constructed by the suspension growth culture method. The established organoids may serve as an effective model for individualized drug screening.

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Section: Discussionmentioning

confidence: 99%

Establishment of gastric cancer organoid and its application in individualized therapy

et al. 2022

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Section: Outlook For Future Research Avenuesmentioning

confidence: 99%

“…In particular, patient-derived organoids offer a valuable platform to elucidate molecular mechanisms of SRC progression and identify potential treatment targets as it provides a more physiological model [ 74 , 75 ]. The organoid can maintain the genotype and phenotype of the original tumour [ 74 ]. Furthermore, organoids maintain the sensitivity of the original tumour to drugs making it an ideal tool for functional drug screening to identify therapeutic targets for implementation in clinical practice [ 76 ].…”

Section: Outlook For Future Research Avenuesmentioning

confidence: 99%

Current advances in understanding the molecular profile of hereditary diffuse gastric cancer and its clinical implications

Lim

Zhuang

Fitzgerald

2023

J Exp Clin Cancer Res

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Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome attributed to germline CDH1 mutations that carries a high risk for early onset DGC. HDGC raises a significant health issue due to its high penetrance and mortality unless diagnosed early. The definitive treatment is to undergo prophylactic total gastrectomy which is associated with significant morbidity., highlighting the urgent need for alternative treatment methods. However, there is limited literature examining potential therapeutic strategies building on emerging insights into the molecular basis of progressive lesions in the context of HDGC. The aim of this review is to summarise the current understanding of HDGC in the context of CDH1 pathogenic variants followed by a review of the proposed mechanisms for progression. In addition, we discuss the development of novel therapeutic approaches and highlight pertinent areas for further research. A literature search was therefore performed for relevant studies examining CDH1 germline variants, second-hit mechanisms of CDH1, pathogenesis of HDGC and potential therapeutic strategies in databases, including PubMed, ScienceDirect and Scopus. Germline mutations are mostly truncating CDH1 variants affecting extracellular domains of E-cadherin, generally due to frameshift, single nucleotide variants or splice site mutations. A second somatic hit of CDH1 most commonly occurs via promoter methylation as shown in 3 studies, but studies are limited with a small sample size. The multi-focal development of indolent lesions in HDGC provide a unique opportunity to understand genetic events that drive the transition to the invasive phenotype. To date, a few signalling pathways have been shown to facilitate the progression of HDGC, including Notch and Wnt. In in-vitro studies, the ability to inhibit Notch signalling was lost in cells transfected with mutant forms of E-cadherin, and increased Notch-1 activity correlated with apoptosis resistance. Furthermore, in patient samples, overexpression of Wnt-2 was associated with cytoplasmic and nuclear β-catenin accumulation and increased metastatic potential. As loss-of-function mutations are challenging to target therapeutically, these findings pave the way towards a synthetic lethal approach in CDH1-deficient cells with some promising results in-vitro. In future, if we could better understand the molecular vulnerabilities in HDGC, there may be opportunities to offer alternative treatment pathways to avoid gastrectomy.

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“…Subsequently, the clinical uses of these mechanisms were tested by using tumor organoids derived from CRC patients harboring differential and diverse mutations [ 5 ]. Tumor organoids derived from mouse or patient tumor cells are a powerful model for cancer studies [ 79 , 80 ].…”

Section: Drug Studymentioning

confidence: 99%

Review on Advanced Cancer Modeling for a Cancer Study

Cho¹

2022

CIMB

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Intensive efforts to develop anti-cancer agents have been made for over 60 years. However, cancer is still considered a lethal disease. To study the best anti-cancer agents for improving the survival rates of cancer patients, many researchers have focused on establishing advanced experimental applications reflecting on the biomimetics of cancer patients involving the heterogeneity of cancer cells. The heterogeneity of cancer cells, which are derived from various clones and affected by different environments, presents different genetic backgrounds and molecular characteristics attributed to the differential responses to cancer therapies, and these are responsible for the resistance to cancer therapies, as well as for recurrence following cancer treatments. Therefore, the development of advanced applications for the cancer patient is expected to help the development of more effective anti-cancer agents. The present review evaluates recently developed cancer models encompassing the heterogeneity of cancer cells, which present similar morphological architecture, genetic backgrounds, and molecular characteristics to corresponding patient tumor tissues.

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Tumor organoids: applications in cancer modeling and potentials in precision medicine

Cited by 105 publications

References 204 publications

Establishment of gastric cancer organoid and its application in individualized therapy

Establishment of gastric cancer organoid and its application in individualized therapy

Current advances in understanding the molecular profile of hereditary diffuse gastric cancer and its clinical implications

Review on Advanced Cancer Modeling for a Cancer Study

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