Phenotypic screening using large‑scale genomic libraries to identify drug targets for the treatment of cancer (Review)

Abstract

During malignant progression to overt cancer cells, normal cells accumulate multiple genetic and non-genetic changes, which result in the acquisition of various oncogenic properties, such as uncontrolled proliferation, drug resistance, invasiveness, anoikis-resistance, the ability to bypass oncogene-induced senescence and cancer stemness. To identify potential novel drug targets contributing to these malignant phenotypes, researchers have performed large-scale genomic screening using various in vitro and in vivo screening models and identified numerous promising cancer drug target genes. However, there are issues with these identified genes, such as low reproducibility between different datasets. In the present study, the recent advances in the functional screening for identification of cancer drug target genes are summarized, and current issues and future perspectives are discussed.

Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer

“…We selected these cells by flow cytometry sorting according to their high DDAO content, deemed LT+ cells. This experiment showed that LT+ cells grow slower and respond less to chemotherapy than non-separated control cells or LT− cells [92,97,98]. We postulated that this is the reason for the resistance observed in some treatments.…”

Discovery of 5,6-Bis(4-methoxy-3-methylphenyl)pyridin-2-amine as a WSB1 Degrader to Inhibit Cancer Cell Metastasis

“…13 Hz, 1H), 3.83 (s, 3H), 2.12 (s, 3H). 13 (15). To a solution of 6bromopyridin-2-amine (28.7 mmol) in 100 mL of dry dichloromethane was added NBS (28.9 mmol) slowly.…”

“…Alternatively, phenotypic screening is a promising strategy for small-molecule drug discovery, especially for those lacking essential information on targets. To date, cell-based phenotypic screening of structurally diverse compounds has delivered many hit/lead compounds. − As part of our continued interest in the area of phenotypic screening − and anticancer drug discovery, − the results of our further studies implied that the function of WSB1 promoting cell migration may not be cell-line-specific, so we started with the phenotypic function of compounds using wound-healing and transwell assay against different cell lines for the enrichment of compounds with antimigration potential. This was followed by a mechanism study to demonstrate whether the active compounds exert their effects through modulating the WSB1-RhoGDI2 signal pathway.…”

Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome

“…Two classic approaches, namely (i) target-based ( Kourbeli et al., 2021 ; Suenaga et al., 2021 ; Swinney, 2013 ) and (ii) whole-cell based ( i.e., phenotypic) screening are used to find hits for drug development ( Ege et al., 2021 ; Love and McNamara, 2021 ; Sato, 2020 ; Swalley, 2020 ). Modes of action for drugs discovered by target-based approaches are presumed to arise from the engagement of a known target in cells.…”