Patient-derived xenograft (PDX) models, applications and challenges in cancer research

Abdolahi, Shahrokh; Ghazvinian, Zeinab; Muhammadnejad, Samad; Saleh, Mahshid; Aghdaei, Hamid Asadzadeh; Baghaei, Kaveh

doi:10.1186/s12967-022-03405-8

Cited by 147 publications

(106 citation statements)

References 145 publications

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“…This is similarly reflected in the results of Oberg et al, who explored the use of linear mixed‐effects models with complex correlation structures in the context of ovarian cancer PDX studies 20 . Additional work has examined the need for unified frameworks of PDX studies and their evaluation to better ensure replicability and optimal use of study data 5,21,22 …”

Section: Discussionmentioning

confidence: 95%

“…The PDX approach involves the direct implantation of human tissue samples into mice, where the mice are assigned to treatment groups then tumor volumes are measured over multiple weeks. This direct implantation into mice may allow for more heterogeneity than laboratory‐grown tissue samples, 1,2,5 and therefore the results may be more directly applicable to human patients.…”

Section: Introductionmentioning

confidence: 99%

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Assessing the performance of different outcomes for tumor growth studies with animal models

Patten

Blatchford

Strand

et al. 2022

Anim Models and Exp Med

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The consistency of reporting results for patient‐derived xenograft (PDX) studies is an area of concern. The PDX method commonly starts by implanting a derivative of a human tumor into a mouse, then comparing the tumor growth under different treatment conditions. Currently, a wide array of statistical methods (e.g., t‐test, regression, chi‐squared test) are used to analyze these data, which ultimately depend on the outcome chosen (e.g., tumor volume, relative growth, categorical growth). In this simulation study, we provide empirical evidence for the outcome selection process by comparing the performance of both commonly used outcomes and novel variations of common outcomes used in PDX studies. Data were simulated to mimic tumor growth under multiple scenarios, then each outcome of interest was evaluated for 10 000 iterations. Comparisons between different outcomes were made with respect to average bias, variance, type‐1 error, and power. A total of 18 continuous, categorical, and time‐to‐event outcomes were evaluated, with ultimately 2 outcomes outperforming the others: final tumor volume and change in tumor volume from baseline. Notably, the novel variations of the tumor growth inhibition index (TGII)—a commonly used outcome in PDX studies—was found to perform poorly in several scenarios with inflated type‐1 error rates and a relatively large bias. Finally, all outcomes of interest were applied to a real‐world dataset.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Assessing the performance of different outcomes for tumor growth studies with animal models

Patten

Blatchford

Strand

et al. 2022

Anim Models and Exp Med

View full text Add to dashboard Cite

show abstract

“…This nanobody-based immunotoxin was extensively tested its activity in vitro and in vivo, showing superb anti-proliferation effect on CDH17-overexpressing gastric cancer cell lines, and significantly inhibits the tumor growth and prolongs the survival in CDH17-positive CDX and PDX models. PDX model is becoming a type of popular and reliable animal model for drug evaluation since it maintains the important characteristics of parental patient tumors, such as molecular phenotype, tumor heterogeneity, tumor microenvironment/structure and similar response to tested drugs [ 35 , 60 ]. These strengths make PDX model more useful for prediction of therapeutic response than conventional CDX model.…”

Section: Discussionmentioning

confidence: 99%

CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

et al. 2022

Biomater Res

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Background It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody-based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer. Graphical Abstract

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“…In ectopic models, tumor cells are injected subcutaneously into the flank or back of the mouse. In contrast, in orthotopic models, tumor cells are often grafted onto the tongue of the mouse [ 70 , 153 ]. Implanting human tumor cells, CDX, or tumor tissue, PDX, into humanized mice based on the human immune system can better simulate the human tumor microenvironment.…”

Section: Humanized Mouse Modelsmentioning

confidence: 99%

Mouse Models for Immune Checkpoint Blockade Therapeutic Research in Oral Cancer

Chiu

Tan

2022

IJMS

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The most prevalent oral cancer globally is oral squamous cell carcinoma (OSCC). The invasion of adjacent bones and the metastasis to regional lymph nodes often lead to poor prognoses and shortened survival times in patients with OSCC. Encouraging immunotherapeutic responses have been seen with immune checkpoint inhibitors (ICIs); however, these positive responses to monotherapy have been limited to a small subset of patients. Therefore, it is urgent that further investigations into optimizing immunotherapies are conducted. Areas of research include identifying novel immune checkpoints and targets and tailoring treatment programs to meet the needs of individual patients. Furthermore, the advancement of combination therapies against OSCC is also critical. Thus, additional studies are needed to ensure clinical trials are successful. Mice models are advantageous in immunotherapy research with several advantages, such as relatively low costs and high tumor growth success rate. This review paper divided methods for establishing OSCC mouse models into four categories: syngeneic tumor models, chemical carcinogen induction, genetically engineered mouse, and humanized mouse. Each method has advantages and disadvantages that influence its application in OSCC research. This review comprehensively surveys the literature and summarizes the current mouse models used in immunotherapy, their advantages and disadvantages, and details relating to the cell lines for oral cancer growth. This review aims to present evidence and considerations for choosing a suitable model establishment method to investigate the early diagnosis, clinical treatment, and related pathogenesis of OSCC.

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Patient-derived xenograft (PDX) models, applications and challenges in cancer research

Cited by 147 publications

References 145 publications

Assessing the performance of different outcomes for tumor growth studies with animal models

Assessing the performance of different outcomes for tumor growth studies with animal models

CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

Mouse Models for Immune Checkpoint Blockade Therapeutic Research in Oral Cancer

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