RESUMO
The US Food and Drug Administration (FDA) approval of the selective RET inhibitors selpercatinib and pralsetinib has led to a paradigm change in the treatment of RET-altered lung and thyroid cancers through a higher response rate and a more tolerable safety and toxicity profile than multi-kinase inhibitors. Recently, selpercatinib has received a tissue-agnostic FDA approval for all RET-fusion-positive cancers, and pralsetinib has shown pan-cancer activity as well. Given the anticipated increase in the use of both drugs across multiple tumor types, it is crucial to recognize the possible side effects and approaches for their optimal management in order to maximize the clinical benefit for treated patients. In this review, we underscore potential toxicities associated with selective RET inhibitors and discuss strategies to mitigate them.
Assuntos
Neoplasias , Estados Unidos , Humanos , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas c-ret/genéticaRESUMO
The cardiovascular activity of essential oils has been reported. Some studies showed that the main chemical components of these oils contribute to their pharmacological activity. Therefore, the cardiovascular activity of four monoterpenes and one sesquiterpene was evaluated in the present work. In non-anaesthetized normotensive rats, (+)-alpha-pinene, (-)-beta-pinene, (+/-)-citronellol and (+/-)-linalool (1, 5, 10, and 20 mg/kg, i.v.) induced hypotension [maximal effect: (-35 +/- 3)%, (-46 +/- 4)%, (-48 +/- 2)% and (-40 +/- 2)%, respectively; n=6] and tachycardia [maximal effect: (13 +/- 4)%, (16 +/- 7)%, (21 +/- 1)% and (19 +/- 3)%, respectively; n=6] while (-)-a-bisabolol (1, 5, 10, and 20 mg/kg, i.v.) induced hypotension [maximal effect: (-47 +/- 8)%, n=6] and bradycardia [maximal effect: (-57 +/- 3)%]. In conclusion, these results demonstrated that all terpenes tested had hypotensive activity in rats and that the pharmacological effect of the terpene alcohols was more effective than that of the terpene hydrocarbons.
