Patient-Derived Xenograft Models to Improve Targeted Therapy in Epithelial Ovarian Cancer Treatment
Year: 2013
Type: review
Abstract: Despite increasing evidence that precision therapy targeted to the molecular drivers of a cancer has the potential to improve clinical outcomes, high-grade epithelial ovarian cancer (OC) patients are currently treated without consideration of molecular phenotype, and predictive biomarkers that could better inform treatment remain unknown. Delivery of precision therapy requires improved integration of laboratory-based models and cutting-edge clinical research, with pre-clinical models predicting patient subsets that will benefit from a particular targeted therapeutic. Patient-derived xenografts (PDXs) are renewable tumor models engrafted in mice, generated from fresh human tumors without prior in vitro exposure. PDX models allow an invaluable assessment of tumor evolution and adaptive response to therapy. PDX models have been applied to pre-clinical drug testing and biomarker identification in a number of cancers including ovarian, pancreatic, breast, and prostate cancers. These models have been shown to be biologically stable and accurately reflect the patient tumor with regards to histopathology, gene expression, genetic mutations, and therapeutic response. However, pre-clinical analyses of molecularly annotated PDX models derived from high-grade serous ovarian cancer (HG-SOC) remain limited. In vivo response to conventional and/or targeted therapeutics has only been described for very small numbers of individual HG-SOC PDX in conjunction with sparse molecular annotation and patient outcome data. Recently, two consecutive panels of epithelial OC PDX correlate in vivo platinum response with molecular aberrations and source patient clinical outcomes. These studies underpin the value of PDX models to better direct chemotherapy and predict response to targeted therapy. Tumor heterogeneity, before and following treatment, as well as the importance of multiple molecular aberrations per individual tumor underscore some of the important issues addressed in PDX models.
Source: Frontiers in Oncology
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: Ovarian Cancer Research Fund, Australian Government, Australian Cancer Research Foundation, Cancer Australia, Cure Cancer Australia Foundation, Petre Foundation, Medical Research Council, National Health and Medical Research Council, Cancer Council Victoria, Cancer Council NSW, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W2125633887