UNC5C: Novel Gene Associated with Psychiatric Disorders Impacts Dysregulation of Axon Guidance Pathways.

The UNC-5 family of netrin receptor genes, predominantly expressed in brain tissues, plays a pivotal role in various neuronal processes. Mutations in genes involved in axon development contribute to a wide spectrum of human diseases, including developmental, neuropsychiatric, and neurodegenerative disorders. The NTN1/DCC signaling pathway, interacting with UNC5C, plays a crucial role in central nervous system axon guidance and has been associated with psychiatric disorders during adolescence in humans. Whole-exome sequencing analysis unveiled two compound heterozygous causative mutations within the UNC5C gene in a patient diagnosed with psychiatric disorders. In silico analysis demonstrated that neither of the observed variants affected the allosteric linkage between UNC5C and NTN1. In fact, these mutations are located within crucial cytoplasmic domains, specifically ZU5 and the region required for the netrin-mediated axon repulsion of neuronal growth cones. These domains play a critical role in forming the supramodular protein structure and directly interact with microtubules, thereby ensuring the functionality of the axon repulsion process. We emphasize that these mutations disrupt the aforementioned processes, thereby associating the UNC5C gene with psychiatric disorders for the first time and expanding the number of genes related to psychiatric disorders. Further research is required to validate the correlation of the UNC5C gene with psychiatric disorders, but we suggest including it in the genetic analysis of patients with psychiatric disorders.

Off-label use of anti-cancer drugs between clinical practice and research: the Italian experience.

BACKGROUND: Off-label use is the practice of prescribing a drug outside the terms of its official labeling. Worldwide, about 20% of the commonly prescribed medications are off-label, and the percentage increases in specific patient populations, such as children, pregnant women, and cancer patients. Off-label use is particularly widespread in oncology for many reasons, including the wide variety of cancer subtypes, the difficulties involved in performing clinical trials, the rapid diffusion of preliminary results, and delays in the approval of new drugs by regulatory organizations/agencies. OBJECTIVE: The aim of this article is to describe the use of off-label drugs in oncology, with an emphasis on the role of the world's leading regulatory agencies and an assessment of current Italian legislation. CONCLUSION: Off-label drug utilization is essential in oncology when based on evidence. However, off-label drugs must be prescribed in accordance with existing national laws and only when the potential benefit outweighs the potential toxic effects.