Epigenetic-Targeting Inhibitors The category of epigenetic-targeting small molecule inhibitors involves a diverse set of pathways that control gene expression. One of the components of gene expression involves histone deacetylases (HDACs), the enzymes that are key in keeping DNA tightly coiled, which “results in a closed chromatin structure and consequently in suppressed transcription of many genes including tumor suppressor genes” (Kuhlen et al., 2019, p. 5). HDAC inhibitors block the HDAC enzymes, which results in decreased proliferation of malignant cells; this causes cell cycle arrest, leads to tumor cell apoptosis, and slows down cancer progression. With the pathway to malignant transformation blocked, the targeted gene can then turn on and make its specific protein, allowing cell differentiation to occur, and the cell can mature to its specific role, such as becoming a skin cell or liver cell. It is important to remember that tumor cells avoid the process of differentiation. Differentiation allows cells to progress through their natural processes, rather than the malignant ones. Although no HDAC inhibitors have been approved by the U.S. Food and Drug Administration for pediatric use at this time, the HDAC inhibitors panobinostat and vorinostat are currently being investigated in pediatric clinical trials. Summary Returning to the analogy that only certain keys fit in certain doors, and only certain doors open into certain rooms, we see that each small molecule inhibitor is the key to stopping a malignant cellular process. Each inhibitor affects only certain pathways and processes. Understanding the mechanism inside the cell will be essential to understanding the processes and uses for each of these new small molecule inhibitors.
Administration Intravenous
Currently two small molecule inhibitors are given intravenously: bortezomib (a proteasome inhibitor) and temsirolimus (an mTOR inhibitor). Bortezomib should be administered as a rapid intravenous push over 3 to 5 seconds (Lexicomp). Temsirolimus is administered as a 30-minute infusion. Premedication with diphenhydramine is recommended before temsirolimus infusions because of the risk of hypersensitivity reactions. Temsirolimus should be administered through non-diethylhexylphthalate (DEHP) tubing using an inline filter (Lexicomp). Subcutaneous Bortezomib can be given subcutaneously. Studies have shown that when it is given by the subcutaneous route, the incidence of peripheral neuropathies is decreased. A survey by Martin and colleagues (2015) of the administration practices of nurses who often administered subcutaneous bortezomib offered these suggestions to minimize skin reactions at the site of injection:
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Pediatric Chemotherapy and Biotherapy Provider Renewal (2021–2023) • © 2021 APHON
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