Patient-Derived Xenograft: An Adjuvant Technology for the Treatment of Metastatic Disease

Abstract

The occurrence of metastases severely affects prognosis for patients with cancer, making metastatic disease a daily societal challenge. Because of resistance to drugs, the potential curability with chemotherapy at the metastatic stage remains low. Large genomic analyses to identify new targets have their limitations due to intratumor heterogeneity when they are performed on tumor samples from primary tumors and because the functional value of molecular abnormalities in a cancer is usually not known. Additional tools are thus required for the development of new anticancer agents. The use of preclinical models is a key component of translational research in oncology. For four decades, xenograft models of human cancer cell lines injected subcutaneously in immunocompromised mice have been widely used, with disappointing results for predicting the clinical benefit of a new drug. Patient-derived xenografts are preclinical models rediscovered as innovative pharmacological tools, both for the preclinical development of anticancer drugs and as individual models for personalized treatment of metastatic disease. Here, we review the recent progress reported using patient-derived xenografts for the treatment of metastatic disease, and discuss the feasibility of their implementation in daily oncological care.

Colon cancers carrying BRAF V600E and β-catenin T41A activating mutations are resistant to numerous common anticancer drugs

“…PDX have emerged as a reliable tool for the preclinical development of cancer therapeutics, and have been demonstrated to overcome the limitations of cancer cell lines and xenograft animal models (19,20). There have been several publications on the establishment of PDCCX mouse models (21)(22)(23)(24).…”

“…These deficiencies cause significant setbacks in cancer therapeutic development Colon cancers carrying BRAF V600E and β-catenin T41A activating mutations are resistant to numerous common anticancer drugs and result in financial and human losses. The emergence of patient-derived cancer xenograft (PDX) models may provide a reliable alternative to cancer cell xenografts for the development of cancer drugs (18)(19)(20). However, there have been no previous reports on the establishment of a CRC PDX model; thus, the present study aimed to establish and characterize a specific CRC PDX mouse model for drug testing.…”

Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer

“…10Y13 Certain experimental conditions, such as orthotopic grafting and subrenal capsular (SRC) grafting, may significantly increase this rate. 14,15 Enhancing the engraftment rate has always been a great concern in establishing PDTX.…”

Current status and perspectives of patient-derived xenograft models in cancer research

“…CCLX models are not adequate for preclinical development of anti-cancer agents because most human cancer cell lines do not accurately reflect human malignant tumors [74]. In contrast, PDX models can better recapitulate each individual patient’s cancer pathology.…”