Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice

Abstract

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential toxicities and adverse drug reactions. Although clinicians often consider pharmacovigilance a non-priority area, it highlights the risk/benefit ratio, an essential factor, especially for these advanced therapies, which represent the most innovative and promising horizon in oncology.

Keywords: cancer; genetic therapy; pharmacovigilance; targeted therapy.

Figure 1

(a) Genetic therapy involves the interaction between pharmacological molecules and the genetic material of the cell; (b) Targeted therapy involve specific sites to interact with molecular targets in the cell. BCR-ABL: Breakpoint Cluster Region-Abelson gene; nRTKi: Non-Receptor Tyrosine Kinase inhibitors; RTKi: Receptor Tyrosine Kinase inhibitors; VEGFR: Vascular Endothelial Growth Factor Receptor; EGFR: Epidermal Growth Factor Receptor; PDGFR: Platelet-Derived Growth Factor Receptor; FGFR: Fibroblast Growth Factor Receptor; CDKi: Cyclin-Dependent Kinase inhibitors; PARPi: Poly Adenosine diphosphate-Ribose Polymerase inhibitors; MHCI: Major Histocompatibility Complex; PD-1: Programmed cell Death Protein 1; CTLA-4: Cytotoxic T-Lymphocyte Antigen 4; CAR: Chimeric Antigen Receptor; ADCC: Antibody-Dependent Cellular Cytotoxicity. (c) Pictorial rappresentation of the workflow of the International sistem of pharmacovigilance. Spontaneous reports of ADRs (adverse drug reactions) are collected from international databases (Vigibase, FAERS system and Eudravigilance) in order to generate alerts and implement post-marketing drug surveillance.