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genomic landscape of their parent tumors. Ji et al. used potential for translational research and drug discovery.
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liver cancer organoids in a drug-proteomic framework At the same time, PDAC has limited efficacy on immune
to advance precise oncology. Scientists have established a checkpoint blocking therapy due to the inhibition of effector
patient-derived liver cancer organoids biobank (LICOB) T cell function. To combat this immunosuppressive tumor
that comprehensively represents the histological and type, scientists established a new model of T cell-integrated
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molecular characteristics of various liver cancer types pancreatic tumor organoid. The organoids incorporated
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determined through multi-group analysis. Proteomic with T cells effectively represent the characteristics observed
analysis of LICOB identified proliferative and metabolic in primitive tumors. In a drug screening utilizing PDA
subtypes in liver cancer pertinent to patient prognosis. organoids, scientists evaluated the epigenetic inhibitors
High-throughput drug screening of 76 drugs with LICOB ITF2357 and I-BET151, which showed significantly
revealed different response patterns for each cancer enhanced anti-tumor effects when combined with anti-PD-
subtype. Therefore, this study provides a comprehensive 1-based therapies. This study dramatically demonstrates
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view of drug responses, actionable targets, and resistance the research prospects of combining organoids and tumor
mechanisms in drug proteomics methodologies. In immunotherapy. In addition, the HOPE trial is a pilot
addition, some studies integrate organoids with animal feasibility trial of personalized treatment using organoids
models to enhance their relevance. Qiu et al. developed to test drug sensitivity and its correlation with clinical
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a novel approach for creating a mouse model of HCC outcomes. This prospective trial assessed the feasibility of
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that incorporates human tumors and simulate the tumor generating PDO in real time from PDAC patients using a
microenvironment of clinical patients. Scientists used limited number of biopsy samples collected during routine
luciferase-expressing Huh7 cells, human iPSC-derived clinical practice. In an attempt to evaluate PDO impacts
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endothelial cells (iPSC-EC), and human iPSC-derived on donors’ responses to traditional anti-cancer drugs and
mesenchymal cells (iPSC-MC) to generate 3D sheet- develop a model to predict disease control, Grossman et al.
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like human HCC organoids in vitro and implant them found that PDO can aid in drug sensitivity profiling and
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into the fragmented livers of immunodeficient mice. personalization of treatment options within 12 – 16 weeks
Traditional methods for establishing liver cancer xenograft after biopsy. 39
models have limitations such as low implantation rates,
uncontrolled tumor sizes, and a propensity for off-target 3.4. Breast cancer
tumor development. This novel animal model has the Breast cancer is and will be one of the important diseases
advantages of a high implantation rate, controllable threatening the health of women around the world. At
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tumor size, and practical preservation of the original liver present, breast cancer is classified and treated clinically
microenvironment. The tumor microenvironment in based on the differences in the expression of estrogen
HCC organoids can be modified by adjusting the ratio of receptor (ER), progesterone receptor, and human epidermal
iPSC-EC and iPSC-MC. 35 growth factor receptor 2 (HER2). Common models
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utilized in breast cancer research include cancer cell lines
3.3. Pancreatic cancer and PDXs. The methods exhibit significant limitations due
Pancreatic ductal adenocarcinoma (PDAC) accounts to their high demands for the quantity of primary tumor
for 90% of pancreatic cancers, mainly due to KRAS cells, rendering them inappropriate for high-throughput
mutations. Mutated KRAS genes stimulate tumor cell drug screening. One study established a PDO biobank
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proliferation, migration, transformation, survival; facilitate using samples from breast cancer patients that faithfully
escape from tumor immune surveillance; and reprogram preserved the histological and genetic characteristics of
cell metabolism during cancer development. A recent their parental tissues. To assess the model’s feasibility in
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study by Duan et al. developed a group of homologous predicting patient drug responses within clinical practice,
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mouse pancreatic organoids containing common PDAC- scientists conducted an in vitro drug screening of breast
driven mutations, including KRAS G12D, TP53 R172H, cancer PDO. PDO successfully predicts drug responses
and SMAD4 deletions. According to a report, out of the in patients, and drug sensitivity testing results of PDO
approximately 6000 compounds screened through PDAC are consistent with actual clinical responses in matched
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organoids, perhexiline maleate was found to selectively patients in most cases. Therefore, PDO can serve as a
inhibit the growth of PDAC organoids carrying the KRAS valuable platform for evaluating treatment efficacy to
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G12D mutation both in vivo and in vitro. Chemical support and guide drug therapy for individual patients.
and genetic perturbations of the SREBP2 gene can also In addition, another study utilized PDO developed from
attenuate the growth of pancreatic organoids carrying the tissue samples collected before treatment (O-PRE) and
KRAS G12D mutation both in vivo and in vitro. Therefore, after treatment (O-POST) to study tumor evolution
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this study based on high-throughput chemical screening of before and after neoadjuvant chemotherapy and surgery.
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homologous pancreatic cancer organoids has significant Both PDO cultures reproduced the histological and

Volume 1 Issue 2 (2025) 6 doi: 10.36922/OR025050008