Current Update of Patient-Derived Xenograft Model for Translational Breast Cancer Research

Abstract

Despite recent advances in the treatment of patients with breast cancer (BrCa), BrCa remains the third leading cause of cancer death for women in the US due to intrinsic or acquired resistance to therapy. Continued understanding of gene expression profiling and genomic sequencing has clarified underlying intratumoral molecular heterogeneity. Recently, the patient-derived xenograft (PDX) models have emerged as a novel tool to address the issues of BrCa genomics and tumor heterogeneity, and to critically transform translational BrCa research in the preclinical setting. PDX models are generated by xenografting cancer tissue fragments obtained from patients to immune deficient mice, and can be passaged into next generations of mice. Generally, in contrast to conventional xenograft using cancer cell lines, PDXs are biologically more stable and recapitulate the individual tumor morphology, gene expression, and drug susceptibility of each patient. PDX may better model the original patient’s tumor by retaining tumor heterogeneity, gene expression, and similar response to treatment. PDX models are thus thought to be more translationally relevant, especially as a drug development tool, because PDXs can capture the genetic character and heterogeneity that exists within a single patient’s tumor and across a population of patients’ tumors. PDX models also hold enormous potential for identifying predictive markers for therapeutic response. It has been repeatedly shown that PDX models demonstrate similar levels of activity as compared to the clinical response to therapeutic interventions. Therefore, this enables identification of therapeutic interventions that can most likely benefit a patient. This allows us to address the issues of BrCa genomics and tumor heterogeneity using PDXs in “pre-clinical” trials. Herein, we reviewed recent scientific development and future perspectives using PDX models in BrCa.

Novel Breast Cancer Brain Metastasis Patient-Derived Orthotopic Xenograft Model for Preclinical Studies

“…The patient-derived xenograft (PDX) model of cancer is created by transplanting tumor tissue in immunodeficient mice at the same (orthotopic) or different (ectopic) anatomic site. PDXs retain genetic, transcriptional and phenotypic features of the original tumor even after long-term continuous passage in vivo [16][17][18][19][20][21], and they have been used successfully to develop new therapies for cancers [22,23]. Subcutaneous breast cancer PDXs are often used for pre-clinical drug screening because both tumor transplantation and tumor tracking are easy.…”

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor

“…Patient-derived xenograft (PDX) models are more translational than immortalized cell line-derived models because they maintain features that are present in the original patient tumor [52,53]. Because MBC is a rare malignancy, there are fewer available model systems to study this disease compared to other breast cancer subtypes; it is crucial to develop new PDX models for MBC.…”

Organoid of ovarian cancer: genomic analysis and drug screening

“…PDX has been established from various types of cancers [12] and has advantages, such as retention of the interaction between tumors and tissues and good representation of the nature of tumors. In the established PDXs of melanoma, breast cancer, and pancreatic cancer, the chemotherapy response is similar to that from the patient's source and could accurately reflect the natural state of the tumor [13,14]. Cytogenetic analysis revealed that compared with cell lines, PDX retains the chromosome structure of tumor tissues [15].…”