Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review

Abstract

Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.

Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization

“…Previously, we reported that 61 CC-PDXs were established from tumor tissues obtained from 98 patients with cervical cancer; the overall enrollment rate was 62.2% [ 23 , 24 , 25 , 26 , 27 ]. A tumor fragment of 1–3 mm 3 may be suitable for establishing CC-PDX [ 28 ]. Hoffman et al reported the implantation of 3–5 mm tumor fragments into SCID mice; however, no viable tumors were observed [ 23 ].…”

“…In the current study, no association was observed between engraftment rate and clinical characteristics of the patients; however, all adenocarcinomas failed to grow. In general, tumor fragments obtained from patients with a large tumor size or advanced stage have a higher success rate of transplantation than tumors obtained from patients with less-advanced disease [ 28 ]. Most established CC-PDX is squamous cell carcinoma [ 23 , 24 , 25 , 26 , 27 , 28 ].…”

“…In general, tumor fragments obtained from patients with a large tumor size or advanced stage have a higher success rate of transplantation than tumors obtained from patients with less-advanced disease [ 28 ]. Most established CC-PDX is squamous cell carcinoma [ 23 , 24 , 25 , 26 , 27 , 28 ]. Several authors created CC-PDX of adenocarcinoma; however, the successful rate of adenocarcinoma was lower than squamous cell carcinoma [ 23 , 24 , 25 , 26 , 27 , 28 ].…”

Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

“…Patient-derived xenograft (PDX) models is another valuable animal model which closely resemble the tumor features of patients and retain the molecular and histological features of diseases. A recent systematic review of PDX of cervical cancer revealed among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2% (0% to 75%) [ 142 ]. No correlation was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis.…”

Advances in Gynecological Cancers

“…Furthermore, this Special Issue included a review [ 8 ] with regards to cervical cancer pathogenesis and its potential diagnostic biomarkers and a systematic review [ 9 ] of 10 original studies with respect to the optimal patient-derived xenograft (PDX) models of cervical cancer. We would care to express our sincere gratitude to all the contributors to this Special Issue of Gynecologic Oncology for IJMC, providing their expert contributions, either as experimental or reviewed data, which will assuredly attract the scientific audience’s attention and undoubtedly encourage the publication of further, high-quality, research papers in the second edition of the Special Issue entitled: “Advances in Gynecological Cancers 2.0”.…”