# Special Issue on \"Anticancer Drugs Activity and Underlying Mechanisms\"
## 2 Contributions  
The need of suitable therapies to treat cancer is the \"primum movens\" of the drug discovery process that, as reported by [PERSON] et al. [11], often starts from academic studies that, hopefully, can be translated \"from the bench to the bedside\" and offer a larger and alternative arsenal to fight cancer. From this point of view, the combined use of in silico and in vivo studies is essential in medicinal chemistry in order to identify putative targets and to explore the anticancer properties of newly synthesized molecules [12] in a given cell modelprior to proceeding towards in vivo studies. Amongst them, the metal complexes, following the successful employment of _Cisplatin_ in cancer treatment, has attracted the attention of many researchers because of their different chemical and biological properties [13; 14]. In this context, two research studies and one review paper published in this Special Issue are representative of this idea. The first, by [PERSON] et al. [15] reported a series of ferrocene derivatives from the general formula [Fe(\(\eta^{5}\)-C\({}_{5}\)H\({}_{4}\)CH\({}_{2}\)(p-C\({}_{6}\)H\({}_{4}\))CH\({}_{2}\)(N-het))\({}_{2}\)], which bear either substituted or unsubstituted saturated five- and six-membered nitrogen-containing heterocycles that are able to inhibit the cervical cancer cell growth, with or without the contemporaneous exposure to ionizing radiation. The authors demonstrated that these complexes possessed higher anticancer activity than _Cis_platin, which was used as reference, and that the exposure to an ionizing radiation increased the anticancer properties, probably because of a radiosensitizing phenomenon that should be further investigated. Cervical cancer cells treated with the lead ferrocene complex underwent intrinsic apoptosis and autophagy with ROS levels increase, as demonstrated by flow cytometry, immunofluorescence, and Western blotting studies. Most importantly, the lead complex exhibited a mild cytotoxic effect on the normal cell lines, which were used as controls, revealing a better cytotoxic profile than _Cis_platin. The second, by [PERSON] et al. [16], describes the study of some N-heterocyclic carbene (NHC)-gold(I) complexes, whose multiple biological activities have already been described [14; 17; 18; 19], disclosing another important target, namely the intracellular actin, and demonstrating that these complexes hamper actin polymerization by means of docking simulations, immunofluorescence, and direct enzymatic assays. These studies highlight the multi-target potential of NHC-gold(I) complexes, whose anticancer properties come together with negligible cytotoxic effects on the normal cells, paving the way to further modifications with the goal of obtaining new and effective anticancer drugs. This even more topical field of research has been reviewed by [PERSON] et al. [20] in detail, who summarized the most salient and up to date papers related to antitumor activity, particularly in terms of breast cancer treatment, drug delivery systems, nanosystems, and complexes based on gold. The authors highlighted how gold-based systems are able to overcome _Cis_platin resistance and its dramatic toxic effects, indicating a desirable therapy personalization that may offer a targeted and more effective treatment and less side effects. An interesting contribution to the area of drug repurposing against cancer has been made by [PERSON] et al. [21], who reported a library of thalidomide analogs. Thalidomide, a historically well-known drug, has recently been repurposed for its anticancer, antiangiogenic, and immunomodulatory actions, and several analogs with improved efficacy and reduced toxicity have been proposed [22; 23]. In this paper, the authors reported the anticancer properties of phthalimide derivatives in a panel of cancer cell lines, mostly against A2058 melanoma cells, individuating a lead compound that is able to block melanoma cell growth by interfering with the tubulin network.