Molecular Diagnostics in Clinical Oncology

Abstract

There are multiple applications of molecular tests in clinical oncology. Mutation analysis is now routinely utilized for the diagnosis of hereditary cancer syndromes. Healthy carriers of cancer-predisposing mutations benefit from tight medical surveillance and various preventive interventions. Cancers caused by germ-line mutations often require significant modification of the treatment strategy. Personalized selection of cancer drugs based on the presence of actionable mutations has become an integral part of cancer therapy. Molecular tests underlie the administration of EGFR, BRAF, ALK, ROS1, PARP inhibitors as well as the use of some other cytotoxic and targeted drugs. Tumors almost always shed their fragments (single cells or their clusters, DNA, RNA, proteins) into various body fluids. So-called liquid biopsy, i.e., the analysis of circulating DNA or some other tumor-derived molecules, holds a great promise for non-invasive monitoring of cancer disease, analysis of drug-sensitizing mutations and early cancer detection. Some tumor- or tissue-specific mutations and expression markers can be efficiently utilized for the diagnosis of cancers of unknown primary origin (CUPs). Systematic cataloging of tumor molecular portraits is likely to uncover a multitude of novel medically relevant DNA- and RNA-based markers.

Keywords: carcinoma of unknown primary site; hereditary cancer syndromes; liquid biopsy; molecular diagnostics; predictive markers; review.

Figure 1

Molecular diagnostics in oncology. There are several major avenues in cancer medicine, which utilize molecular-based assays. Testing for hereditary cancer syndromes is now routinely used both for identification of persons at-risk and for personalization of systemic treatment. There is a number of predictive tests involving either the analysis of individual drug targets or identification of specific tumor phenotypes, which aid the choice of anticancer drugs. Monitoring of malignant disease can be achieved through molecularly-driven detection of residual tumor fragments; it is anticipated that liquid biopsy will serve as an instrument for early cancer diagnosis and screening in the future. Recent developments in the mutation testing and RNA analysis offer novel tools for diagnosis of cancers of unknown primary site.