Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.

The cytochrome P450 (CYP) enzyme family is the major enzyme system catalyzing the phase I metabolism of xenobiotics, including pharmaceuticals and toxic compounds in the environment. A major part of the CYP-dependent xenobiotic metabolism is due to polymorphic and inducible enzymes, which may, quantitatively or qualitatively, alter or enhance drug metabolism and toxicity. Drug–drug interactions are major mechanisms caused by the inhibition and/or induction of CYP enzymes. Particularly, CYP monooxygenases catalyze hydroxylation reactions to form hydroxylated metabolites. The secondary metabolites are sometimes as active as the parent compound, or even more active. The aim of this review is to summarize some of the significative examples of common drugs used for the treatment of diverse diseases and underline the activity and/or toxicity of their metabolites.

Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progression in vitro and in vivo and synergizes with radiotherapy