How 3D imaging of patient-derived cancer cells improves drug efficacy research
As one of the deadliest cancers, non-small cell lung carcinoma (NSCLC) is a prime candidate for personalized medicine. However, the difficulty and expense of creating cancer cell models for drug testing has proven prohibitive, and the relatively low biological relevance of cancer-derived cell lines leads to ineffective treatment strategies.
In a recently published issue of Nature’s online journal Scientific Reports, researchers from CRL have proposed 3D modeling techniques for patient-derived xenografts (PDX). These tumor models are much more effective platforms for drug testing than 2D cultivated cell lines due to their closer mimicry of the cancer’s cellular diversity and the patient’s genome.
“The major drawback of cancer cell lines is their monoclonal origin, or lack of heterogeneity,” said Dr. Julia Schueler, Head of In Vivo Operations in CRL’s Freiburg, Germany laboratory. “Patient tumors are heterogeneous, e.g. composed of multiple sub-clones with different characteristics. PDX do reflect this heterogeneity as they never underwent a clonal selection process (or at least not very stringent one).”
The PDX cells, when implanted in their immunodeficient mouse hosts, create cancerous conditions that are much closer to the patient’s biology than models derived from generic cancer cell lines. In the study, researchers were able to determine that the chemotherapy drug docetaxel would be most effective for their particular PDX example by studying the cells in vitro and in vivo.
“In the paper we followed tumor growth of PDX growing in mice, as well as in the 3D culture under treatment with different compounds,” Dr. Schueler said. “Using the image analysis technique we were able to compare the in vivo data with the in vitro data. The comparison revealed that the sensitivity towards the tested compounds in vivo could be predicted by testing them in the 3D in vitro platform.”
The results of the researchers’ work on PDX models and the development of effective 3D imaging techniques is a notable breakthrough for a project that has been funded for the past five years by the EU. The study represents a collaboration between CRL’s team in Freiburg and the University of Turku in Finland, and the findings could lead to more effective and less expensive personalized treatment options for patients with lung cancer.