ABSTRACT
Organotypic in vitro culture of 3D spheroids in an extracellular matrix represent a promising cancer therapy prediction model for personalized medicine screens due to their controlled experimental conditions and physiological similarities to in vivo conditions. As in tumors in vivo, 3D invasion cultures identify intratumor heterogeneity of growth, invasion and apoptosis induction by cytotoxic therapy. We here combine in vitro 3D spheroid invasion culture with irradiation and automated nucleus-based segmentation for single cell analysis to quantify growth, survival, apoptosis and invasion response during experimental radiation therapy. As output, multi-parameter histogram-based representations deliver an integrated insight into therapy response and resistance. This workflow may be suited for high-throughput screening and identification of invasive and therapy-resistant tumor sub-populations.
Subject(s)
Cell Culture Techniques/methods , Neoplasms/diagnostic imaging , Spheroids, Cellular/physiology , Animals , Cell Line, Tumor , Humans , Microscopy, Confocal/methods , Neoplasms/drug therapy , Organ Culture Techniques , Rats , Treatment OutcomeABSTRACT
Most patients that die from cancer do not die due to the primary tumor but due to the development of metastases. However, there is currently still no drug on the market that specifically addresses and inhibits metastasis formation. This lack was, in the past, largely due to the lack of appropriate screening models, but recent developments have established such models and have provided evidence that tumor cell migration works as a surrogate for metastasis formation. Herein we deliver on several examples a rationale for not only testing novel cancer drugs by use of these screening assays, but also reconsider established drugs even of other fields of indication.
ABSTRACT
As the number of novel drugs that have entered the market in oncology has slowed in recent years, there has been a dramatic shift towards new therapeutic approaches. The majority of cancer patients die from metastasis formation, which has prompted the pharmaceutical industry to begin to investigate a new class of agents: anti-metastatics. This review provides an overview of the targets, mechanisms of action, and drug substances currently in the pharma pipeline to inhibit tumor cell migration and metastasis formation.