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.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of the disease (rod-cone dystrophy, polydactyly, obesity, genital abnormalities, renal defects, and learning difficulties) and secondary BBS characteristics (developmental delay, speech deficit, brachydactyly or syndactyly, dental defects, ataxia or poor coordination, olfactory deficit, diabetes mellitus, congenital heart disease, etc.); most of these symptoms may not be present at birth but appear and progressively worsen during the first and second decades of life. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms; however, it is gradually becoming more accessible with the invention of multigene sequencing technologies. Clinical management of BBS is largely limited to a symptomatic treatment. Mouse experiments demonstrate that the most debilitating complication of BBS, blindness, can be rescued by topical gene therapy. There is a published case report describing the delay of BBS symptoms by nutritional compensation of the disease-related biochemical deficiencies. Progress in DNA testing technologies is likely to rapidly resolve all limitations in BBS diagnosis; however, much slower improvement is expected with regard to BBS treatment.

Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.