Table 2.
PDX Model
| Cancer Model | Animal Species | Finding | Reference |
|---|---|---|---|
| Adenoid cystic carcinoma | Zebrafish | The CR/zebrafish model mirrors the PDX mouse model and identifies regorafenib as a potential therapeutic drug to treat this cancer type that mimic the drug sensitivity profile in PDX model. | [147] |
| Breast cancer | Mouse | Through various experimental and computational approaches using human tumors within immunocompromised mice, the lung was found to be the most common site of relapse; lymph nodes and liver were the other most common metastatic sites. | [148] |
| Breast cancer | Zebrafish | They propose an original approach to study the metastatic process and cancer cell aggressiveness comprising the use of patient-derived primary cultures in the in vivo ZF model. | [149] |
| Breast cancer | Mouse | Growth of breast cancer PDX tumors was significantly enhanced by co-transplantation with ADSCs in vivo, and it was weakened when co-transplanted with the adipsin knocked-down ADSCs. | [150] |
| Breast cancer | Mouse | PARP inhibition can have activity beyond germline BRCA1/2 altered tumors, causing regression in a variety of molecular subtypes. | [151] |
| Breast cancer | Mouse | Concurrent inhibition of sfRon and PI3K in breast PDX tumors with wild-type PIK3CA provided durable tumor stasis after therapy cessation, whereas discontinuation of either monotherapy facilitated tumor recurrence. | [152] |
| Cervical cancer | Mouse | In vivo studies with PDXs revealed that TAO significantly decreased tumor weight for both primary squamous cell carcinoma and adenocarcinoma of the cervix. However, this anti-cancer effect was not seen in PDXs with recurrent cancers. | [153] |
| Colon Carcinoma | Mouse | HER2-specific CAR-T cells showed long-term persistence in vivo and effectively eliminated the freshly transplanted tumor tissues. | [154] |
| Colorectal cancer | Mouse | The gluconeogenic enzyme PCK1 enhanced liver metastatic growth by driving pyrimidine nucleotide biosynthesis under hypoxia. Therapeutic inhibition of the pyrimidine biosynthetic enzyme DHODH with leflunomide substantially impaired CRC liver metastatic colonization and hypoxic growth. | [155] |
| Colorectal cancer | Mouse | MAPK and EGFR pathway activations are two major molecular hallmarks of colorectal cancer. Concurrent EGFR and RAF inhibition demonstrated synergistic antitumor activity for colorectal cancer PDX models with a KRAS or BRAF mutation. | [156] |
| Colorectal cancer | Mouse | The combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs. | [157] |
| Colorectal cancer | Mouse | HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. | [158] |
| Colorectal cancer | Mouse | Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. | [159] |
| Colorectal cancer | Mouse | Anti-tumor activity of cabozantinib would be superior to regorafenib in CRC PDX models due to dual inhibition of MET and VEGFR2, as well as potentially other metabolic and autophagy mechanisms. | [160] |
| Esophageal cancer | Mouse | APIO-EE-9 significantly decreased the size of esophageal patient-derived xenograft (PDX) tumors implanted in SCID mice. It is a specific Aurora kinase inhibitor that could be developed as a therapeutic agent against esophageal cancer. | [161] |
| Gastric cancer | Zebrafish | They describe a new in vivo zPDX model of GC. This model can be used to study tumor angiogenesis, cell invasiveness and drug responses in a time-saving and cost-saving manner. | [162] |
| Gastric cancer | Mouse | They demonstrated that microRNA-133a-3p overexpression could block the activation of autophagy to ruin the abnormal glutaminolysis and further inhibit the growth and metastasis of gastric cancer cells | [163] |
| Gastric cancer | Mouse | Knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. | [164] |
| Gastric cancer | Mouse | CAFs-derived LOX at liver metastatic niche of GC promotes niche formation and outgrowth thus predicts poor prognosis. Meanwhile tumor cells in niche secrete TGF-β1 to nourish CAFs and stimulate them to produce more LOX in turn. | [165] |
| Gastric cancer | Mouse | They explored the therapeutic potential of NNT inhibition in PDX models via in vivo siRNA treatment. Silencing NNT significantly suppressed tumor growth and induced cell apoptosis. | [166] |
| Gastric cancer | Mouse | ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression. | [167] |
| Gastric cancer | Mouse | Gastrin inhibited GC growth and enhanced the suppression of GC by cisplatin in mice or PGC cell culture models through activating the ERK-P65-miR23a/27a/24 axis or its components. | [168] |
| Gastric cancer | Mouse | LH inhibited tumorigenicity in gastric cancer through down-regulating the expression of MCL1. And LH combined with HA14–1 (inhibitor of BCL2) exhibited a more significant inhibitory effect than LH alone in vivo. | [169] |
| Gastric cancer | Mouse | In the PDX models with EGFR amplification, mRNA or protein overexpression, cetuximab treatment was associated with a better survival compared with that noted in the untreated group in the PDX models (P<0.05), while the survival was not statistically different in the other cases (P>0.05). | [170] |
| Gastric cancer | Mouse | The anti-tumor effect of trastuzumab was enhanced by its combination with anti-HER3 antibodies (1A5–3D4) in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. | [171] |
| Gastric cancer | Mouse | 124I-trastuzumab was feasible to detect HER2-positive lesions in primary and metastatic gastric cancer patients and to differentiate HER2-positive and HER2-negative lesions quantitatively. | [172] |
| Hepatocellular carcinoma | Mouse | A CDK1 inhibitor (RO3306) in combination with sorafenib acts on hepatocellular carcinoma with a synergistic antitumor growth effect on PDX tumor models, which may be due to its effects on decreasing the liver cancer stem cell stemness via the CDK1/PDK1/β-Catenin signaling pathway. | [173] |
| High-grade serous ovarian cancer | Mouse | CUB-domain containing protein 1 (CDCP1) is over-expressed by the majority of HGSCs. CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer. | [174] |
| Leukemia | Mouse | Zapadcine-1 drastically eliminates the xenografts in both CDX and PDX models of human acute leukemia. And it does not have notable toxic side effects on heart, liver, lung and kidney. | [175] |
| Lung cancer | Mouse | PG545 was highly effective in PDX that did not respond to conventional chemotherapy (cisplatin), while other PDX tumors responded well to cisplatin and to a lower extent to PG545. | [176] |
| Lung cancer | Rat | The severely immunodeficient SD‐RG rats support fast growth of PDX compared with mice, thus holding great potential to serve as a new model for oncology research. | [177] |
| Lung squamous cell carcinoma | Mouse | Combination therapy with a FGFR tyrosine kinase inhibitor and cisplatin reduced tumor growth by decreasing cell proliferation and increasing cell death. | [178] |
| Melanoma | Mouse | Genetic aberration of CDK4 pathway is a frequent event in acral melanoma. Acral melanoma cell lines and PDX containing CDK4 pathway aberrations are sensitive to CDK4/6 inhibitors. | [179] |
| Oesophageal adenocarcinoma | Mouse | APR-246 demonstrated potent antitumour activity in CLX and PDX models, and restored chemosensitivity to a cisplatin/5-fluorouracil-resistant xenograft model. | [180] |
| Ovarian cancer | Mouse | Treatment with an anti-CD20 monoclonal antibody, rituximab, not only inhibited the proliferation of established B-cell lymphoma in SCID mice but also prevented the occurrence of lymphomatous outgrowth in early-passage xenografts. | [181] |
| Ovarian cancer | Mouse | Both the activity of bevacizumab in combination with chemotherapy for the treatment of ovarian tumors and that this antitumor activity can be further improved by the addition of another targeted agents (MEK inhibitor). | [182] |
| Pancreatic cancer | Mouse | The VEGF pathway–mediated angiogenesis might influence tumor implantation as well as the growth in PDXs, thus affecting prognosis in patients or tumor‐bearing mice. | [183] |
| Pancreatic cancer | Mouse | miR-193a stimulated pancreatic cancer cell repopulation and metastasis through modulating TGF-β2/TGF-βRIII signalings, and miR-193a might be a potential therapeutic target for pancreatic cancer repopulation and metastasis. | [184] |
| Pancreatic cancer | Mouse | Adenosine induces apoptosis in pancreatic cancers, and GSK690693 can exert sensitizing effects when applied in combination with adenosine. | [185] |
| Pancreatic cancer | Mouse | They developed apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent which potently inhibited the growth of both established and patient-derived primary pancreatic cancer cells. | [186] |
| Papillary renal cell carcinoma | Mouse | AZD6094 treatment resulted in tumor regressions, whereas sunitinib or crizotinib resulted in unsustained growth inhibition. | [187] |
| Prostate cancer | Mouse | MET in tumor cells is not a persistent therapeutic target for metastatic CRPC, but inhibition of VEGF-R2 and MET in endothelial cells and direct effects on osteoblasts are responsible for cabozantinib-induced tumor inhibition. | [188] |
| Prostatic carcinoma | Mouse | Cyclin D1 loss identifies prostate tumors with small cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis. | [189] |
| Receptor-negative breast cancer | Mouse | Vandetanib treatment could be useful for patients with ER negative breast cancers overexpressing Vandetanib’s main targets. In a PDX model with no expression of RET nor EGFR, Vandetanib slowed tumor growth without inducing tumor regression. | [190] |
| Small cell lung cancer | Mouse | PARP trapping may play an important role in radiosensitization of SCLC cells, as talazoparib was a more effective radiosensitizer compared to veliparib at concentrations chosen to result in equivalent enzymatic inhibition. | [191] |
| Triple-negative breast cancer | Mouse | ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. | [192] |
| Triple-negative breast cancer | Mouse | Capecitabine was effective against 60% of TNBC PDX derived from tumors previously treated with anthracyclines and taxanes, and we identified TYMP and RB1 expression as putative biomarkers predictive of the response to capecitabine. | [193] |
| Triple-negative breast cancer | Mouse | Selinexor is a promising agent in the treatment of TNBC, with enhanced antitumor activity in combination with chemotherapy. | [194] |