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.

Highlights

  • Cervical cancer, caused by persistent infection of human papillomavirus (HPV), ranks the second common cause of cancer-related deaths worldwide [1]

  • Dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumor growth in patient-derived xenograft (PDX) of

  • Phase 2 clinical trial proved the effectiveness of this therapy in treatment-refractory patients with HER2-positive metastatic colorectal cancer [4]

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Summary

Introduction

Cervical cancer, caused by persistent infection of human papillomavirus (HPV), ranks the second common cause of cancer-related deaths worldwide [1]. For early-stage patients, surgical resection or radiotherapy provides a satisfactory prognosis. The patients with advanced-stage or recurrent disease have dismal prognosis [2]. An effective therapy and biomarker determinates of therapeutic response for refractory cervical cancer is expected to be found. Dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumor growth in patient-derived xenograft (PDX) of HER2-amplified tumor [3]. Phase 2 clinical trial proved the effectiveness of this therapy in treatment-refractory patients with HER2-positive metastatic colorectal cancer [4]

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