Chemosensitivity and resistance testing in malignant effusions with focus on primary malignant mesothelioma and metastatic adenocarcinoma

Abstract

AbstractCell based chemosensitivity and resistance testing is an attractive approach that offers functional measurement of drug responseex vivowith the ultimate goal to guide the choice of chemotherapy for various cancers. Thus, it has a great potential to select patients for the optimal treatment option, thereby offering a tool for personalized cancer therapy.Despite several decades of intensive scientific effortsex-vivotests are still not incorporated in the standard of care. Limited access to fresh tumor tissue, unsatisfactory models and single readout as endpoint constitute major hindrance. Thus, establishing and validating clinically useful and reliable model systems still remains a major challenge.Here we present malignant effusions as valuable sources forex-vivochemosensitivity and resistance testing. Accumulation of a malignant effusion in the pleura, peritoneum or pericardium is often the first diagnostic material for both primary malignant mesothelioma and a broad spectrum of metastatic adenocarcinoma originating from lung-, breast-, ovary- and gastro-intestinal organs as well as lymphoma.In contrast to biopsies, in these effusions malignant cells are easily accessible and often abundant. Effusion derived cells can occur dissociated or forming three-dimensional papillary structures that authentically recapitulate the biology of the corresponding tumor tissue and offer models forex vivotesting. In addition, effusions have the advantage of being available prior to or concurrent with the pathological review, thus constituting an excellent source of viable cells for simultaneous molecular profiling, biomarker analysis and for establishing primary cells for studying tumor biology and resistance mechanisms.For a reliable test, however, a careful validation is needed, taking into account the inherited heterogeneity of malignant tumors, but also the complex interplay between malignant and benign cells, which are always present in this setting.