The Melding of Drug Screening Platforms for Melanoma

Abstract

The global incidence of cancer is rising rapidly and continues to be one of the leading causes of death in the world. Melanoma deserves special attention since it represents one of the fastest growing types of cancer, with advanced metastatic forms presenting high mortality rates due to the development of drug resistance. The aim of this review is to evaluate how the screening of drugs and compounds for melanoma has been performed over the last seven decades. Thus, we performed literature searches to identify melanoma drug screening methods commonly used by research groups during this timeframe. In vitro and in vivo tests are essential for the development of new drugs; however, incorporation of in silico analyses increases the possibility of finding more suitable candidates for subsequent tests. In silico techniques, such as molecular docking, represent an important and necessary first step in the screening process. However, these techniques have not been widely used by research groups to date. Our research has shown that the vast majority of research groups still perform in vitro and in vivo tests, with emphasis on the use of in vitro enzymatic tests on melanoma cell lines such as SKMEL and in vivo tests using the B16 mouse model. We believe that the union of these three approaches ( in silico, in vitro , and in vivo ) is essential for improving the discovery and development of new molecules with potential antimelanoma action. This workflow would provide greater confidence and safety for preclinical trials, which will translate to more successful clinical trials and improve the translatability of new melanoma treatments into clinical practice while minimizing the unnecessary use of laboratory animals under the principles of the 3R's.

Anti-Melanoma Activities of Artemisone and Prenylated Amino-Artemisinins in Combination With Known Anticancer Drugs

“…HaCaT cells were chosen as the nonmalignant control due to their ease of propagation, near normal phenotype and general use as an A375 control (Dwivedi et al, 2015;Lewies et al, 2018). The A375 cell line is a melanotic cells line with the BRAF mutation frequently used for in vitro drug screening assays for anti-melanoma drugs (Couto et al, 2019). All reagents were of analytical grade and were obtained from Merck (Darmstadt, Germany) unless stated otherwise.…”

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

“…Numerous high-throughput genomic and proteomic studies comparing healthy and cancerous cells have identified many such potential drug targets [9,12,13]. These putative targets are then subjected to high-throughput screening with libraries of potential drug candidates, such as peptides, antibodies, natural compounds, chemicals, and aptamers [10,[14][15][16][17][18][19][20][21][22]. Selected molecules that specifically bind to the target are considered for further functional validation [17].…”

VWCE as a potential biomarker associated with immune infiltrates in breast cancer

“…This suggests that VWCE may activate or inhibit immune cells infiltrating the tumor, although the underlying mechanism involved is unknown. Macrophages are a group of differentiated immune cells and classify as M1 macrophages and M2 macrophages [ 47 ]. They play an important role in development, homeostasis, and immunity [ 48 ].…”