APHON Pediatric Chemotherapy-Biotherapy Renewal

message as it travels along the pathway. When the destination is reached, the message will be translated, and the cell will respond by performing the specific function that the signal initiated. In malignancy, a disruption occurs along one or more of the signaling pathways, resulting in loss of control. One or more of the “doors” along a pathway malfunctions, resulting in uncontrolled proliferation and loss of programmed cell death–hallmarks of malignant cells. Small molecule inhibitors can target specific malfunctioning doors along the signaling pathway. They block the aberrant signal that is keeping the door from opening and closing correctly, thereby restoring the normal signals that keep the door functioning properly. During the last few years, scientific research has identified many of the doors on signaling pathways and the specific cancers associated with the malfunctioning pathway. After these locations have been identified, further research can focus on finding small molecule inhibitors that will be effective against those targets. As Kuhlen and colleagues (2019, p. 2) expressed it, “These developments may ultimately break with the practice paradigms of ‘one-size-fits-all’ therapy and guide the development of precision/personalized treatment including immunotherapy and targeted (genomic) therapy to offer the ‘right drug for the right patient at the right time,’ even in children.” The following is a brief review of a few intracellular pathways that are important to cancer cells, along with examples of the small molecule inhibitors that can have an impact on those pathways. Intracellular Signaling Kinase Pathways Many of the signaling pathways are named for the protein kinases along that pathway. These protein kinases are the waypoints, or doors, that the signal will pass through as it travels along the pathway. “Protein kinases play a major role in cellular regulation including differentiation, survival, proliferation, metabolism, migrating, and signaling, as well as cell-cell interactions” (Kuhlen et al., 2019, p. 2). Cancer cells often take control of these signaling pathways in order to survive. For example, in the MAP kinase pathway, certain signals attach to the epidermal growth factor receptor (EGFR), and these communications are then transferred from protein to protein inside the cell. After those signals are passed on, they eventually reach the nucleus of the cell, activating genes that control cell division (Anderson et al., 2019). Figure 1 illustrates this mechanism. Dabrafenib is an example of a small molecule inhibitor that targets BRAF kinase mutations along this pathway and the proteins inside the cell that transfer the cell division signals (Novartis, 2020).