The PERMIT guidelines for designing and implementing all stages of personalised medicine research.

Personalised medicine (PM) research programmes represent the modern paradigm of complex cross-disciplinary research, integrating innovative methodologies and technologies. Methodological research is required to ensure that these programmes generate robust and reproducible evidence. The PERMIT project developed methodological recommendations for each stage of the PM research pipeline.

Recommendations for robust and reproducible preclinical research in personalised medicine.

Background: Personalised medicine is a medical model that aims to provide tailor-made prevention and treatment strategies for defined groups of individuals. The concept brings new challenges to the translational step, both in clinical relevance and validity of models. We have developed a set of recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine.

Evaluating Translational Methods for Personalized Medicine-A Scoping Review.

The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine approaches. Two case models were chosen: oncology and brain disorders.

Xenograft Models of Ovarian Cancer for Therapy Evaluation.

The evaluation of novel treatment regimes in ovarian cancer, ranging from cytotoxic agents and targeted therapy to surgery, demands clinically relevant mouse models to mimic human disease. These more advanced preclinical models provide a tool to obtain robust data on the mechanism of action, cytotoxicity and therapeutic efficacy of newly emerging antitumor therapies.In this chapter, we describe how to generate ovarian cancer xenograft models through injection of human tumor cell lines in immunocompromised mice.

Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model.

Purpose: Fluorescence imaging (FLI) using targeted near-infrared (NIR) conjugates aids the detection of tumour lesions pre- and intraoperatively. The optimisation of tumour visualisation and contrast is essential and can be achieved through high tumour-specificity and low background signal. However, the choice of fluorophore is recognised to alter biodistribution and clearance of conjugates and is therefore a determining factor in the specificity of target binding.

The Emerging Role of CD24 in Cancer Theranostics-A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond.

Complete cytoreductive surgery is the cornerstone of the treatment of epithelial ovarian cancer (EOC). The application of fluorescence image-guided surgery (FIGS) allows for the increased intraoperative visualization and delineation of malignant lesions by using fluorescently labeled targeting biomarkers, thereby improving intraoperative guidance. CD24, a small glycophosphatidylinositol-anchored cell surface receptor, is overexpressed in approximately 70% of solid cancers, and has been proposed as a prognostic and therapeutic tumor-specific biomarker for EOC.

CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model.

Background: The completeness of resection is a key prognostic indicator in patients with ovarian cancer, and the application of tumour-targeted fluorescence image-guided surgery (FIGS) has led to improved detection of peritoneal metastases during cytoreductive surgery. CD24 is highly expressed in ovarian cancer and has been shown to be a suitable biomarker for tumour-targeted imaging.

Methods: CD24 expression was investigated in cell lines and heterogenous patient-derived xenograft (PDX) tumour samples of high-grade serous ovarian carcinoma (HGSOC).

CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma.

Background: The survival rate of patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains disappointing. Clinically translatable orthotopic cell line xenograft models and patient-derived xenografts (PDXs) may aid the implementation of more personalised treatment approaches. Although orthotopic PDX reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by lack of appropriate imaging modalities.