A magic drug target: Androgen receptor

Huang

J Cellular Molecular Medi

et al. 2020

The aldo‐keto reductases family 1 member C2 (AKR1C2) has critical roles in the tumorigenesis and progression of malignant tumours. However, it was also discovered to have ambiguous functions in multiple cancers and till present, its clinical significance and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) has been unclear. The aim of this study was to explore the role of AKR1C2 in the tumorigenesis of ESCC. Here, we showed that AKR1C2 expression was found to be up‐regulated in ESCC tissues and was significantly associated with pathological stage, lymph node metastasis and worse outcomes. Functional assays demonstrated that an ectopic expression of AKR1C2 in ESCC cells resulted in increased proliferation, migration and cisplatin resistance, while knockdown led to inversing effects. Bioinformation analyses and mechanistic studies demonstrated that AKR1C2 activated the PI3K/AKT signalling pathway, furthermore, the inhibitor of PI3K or the selective inhibitor of AKR1C2 enzyme activity could reverse the aggressiveness and showed synergistic antitumour effect when combined with cisplatin, both in vitro and in vivo. In conclusion, Our findings revealed that AKR1C2 could function as an oncogene by activating the PI3K/AKT pathway, as a novel prognostic biomarker and/or as a potential therapeutic target to ESCC.

Section: Discussionsupporting

confidence: 71%

AKR1C2 acts as a targetable oncogene in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Huang

J Cellular Molecular Medi

et al. 2020

“…Finally, because of the high expression of AR in CTCs from TNBC patients, we explored the effect of pharmacological inhibition of the AR pathway, which is a common therapeutic strategy in AR-dependent tumors such as prostate cancer [21]. To that end, we treated the MDA-MB 231 model cell line with Abiraterone, which inhibits androgen biosynthesis by CYP17 blockage.…”

Section: Ctc Profiling Helps To Identify Therapeutic Targets Such As mentioning

confidence: 99%

Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells

Abreu

Cabezas-Sáinz

Pereira-Veiga³

et al. 2020

JCM

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients’ outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer.

“…Current therapeutics include steroidal and non-steroidal anti androgens targeting typically LBD of AR [90][91][92] . Although other modulators targeting another domain are speedily investigated and shows beneficial preclinical profiles [84,93] . Shi et al [92] developed and synthesized a series of steroidal pyridines derivative through the base promoted three component reaction and preliminarily evaluated for their anti-proliferative activity against cancer cell lines.…”

Section: Androgen Receptor (Ar) Inhibitormentioning

confidence: 99%

Pyridine Moiety: Recent Advances in Cancer Treatment

Sahu¹,

Mishra²,

Kumar³

et al. 2021

ijps

Pyridine is an imperative pharmacophore, a privileged scaffold and an exceptional heterocyclic system in the field of drug discovery which provides many opportunities in study/explore this moiety as an anticancer agent by acting on various receptors of utmost importance. Several pyridine derivatives are reported to inhibit tubulin polymerization, androgen receptors, human carbonic anhydrase, kinase, topoisomerase enzyme and many other targets for controlling and curing global health issue of cancer. Now a days in combination with other moieties researchers are focusing for development of pyridine new entities for the treatment of cancer. This review throws light on recent biological expansions of pyridine along with their structure activity relationships/molecular docking to deliver association between various synthesized newer derivatives and receptor sites.