Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far.

A Facile, Transfection-Free Approach to siRNA Delivery in In Vitro 3D Spheroid Models.

Cell culture has long been essential for preclinical modeling of human development and disease. However, conventional two-dimensional (2D) cell culture fails to faithfully model the complexity found in vivo, and novel drug candidates that show promising results in 2D models often do not translate to the clinic. More recently, three-dimensional (3D) cell culture models have gained popularity owing to their greater physiological relevance to in vivo biology.

Comparison of two supporting matrices for patient-derived cancer cells in 3D drug sensitivity and resistance testing assay (3D-DSRT).

Central to the success of functional precision medicine of solid tumors is to perform drug testing of patient-derived cancer cells (PDCs) in tumor-mimicking ex vivo conditions. While high throughput (HT) drug screening methods have been well-established for cells cultured in two-dimensional (2D) format, this approach may have limited value in predicting clinical responses. Here, we describe the results of the optimization of drug sensitivity and resistance testing (DSRT) in three-dimensional (3D) growth supporting matrices in a HT mode (3D-DSRT) using the hepatocyte cell line (HepG2) as an example.

Protocol for 3D drug sensitivity and resistance testing of patient-derived cancer cells in 384-well plates.

Establishment of drug testing of patient-derived cancer cells (PDCs) in physiologically relevant 3-dimensional (3D) culture is central for drug discovery and cancer research, as well as for functional precision medicine. Here, we describe the detailed protocol allowing the 3D drug testing of PDCs - or any type of cells of interest - in Matrigel in 384-well plate format using automation. We also provide an alternative protocol, which does not require supporting matrices.

Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status.

Objective: A major challenge in the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) is lack of effective therapies. Much of ongoing research on drug candidates relies on HGSOC cell lines that are poorly documented. The goal of this study was to screen for effective, state-of-the-art drug candidates using primary HGSOC cells.