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Cancer Biology and Genetics for Non-Biologists
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
Cell signalling is very complex. The sending of an initial signal to the final outcome induced by the signal usually involves many proteins and hence genes. The route taken to achieve the outcome is via a cell signalling pathway. For example, the MAPK/ERK pathway, also known as the Ras/Raf/MEK/ERK pathway, plays a significant role in cell growth and differentiation (the process where immature cells develop to reach their specialised form and function). The MAPK family is a set of mitogen-activated protein kinases (a kinase is a particular type of enzyme) produced by particular genes such as MAPK1, MAPK3, …MAPK15. These have other names, for example, MAPK1 is also known as ERK. A very simplified version of the MAPK/ERK pathway is,
A patent review of cyclin-dependent kinase 7 (CDK7) inhibitors (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Markéta Kovalová, Joseph Peter Baraka, Václav Mik, Radek Jorda, Lei Luo, Hao Shao, Vladimír Kryštof
YPN-005 is highly selective for CDK7 from Yungjin Pharmaceutical with an IC50 of 31 nM and inhibited 7 other kinases over 90% at 1 µM in a 468 kinase panel screen, including CDK13, CDK19, CSNK1A1, CSNK1D, CSNK1E, MAPK15, and MAPK10 [60]. YPN-005 showed potent antiproliferative effects in SCLC cells, cisplatin- or etoposide-resistant cells, and organoids derived from SCLC patients. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the RNAP II CTD and significantly inhibited tumor growth in xenograft models established from the SCLC cell line H209 and cisplatin- or etoposide-resistant H209 cells. Another study [61] showed its antileukemic potential both in vitro and in vivo. YPN-005 induced apoptosis and suppressed the expression of c-MYC, FLT3 and STAT5. An ex vivo proliferation inhibition assay in primary leukemic cells also showed higher sensitivity in AML cells with FLT3-ITD mutation.
Deciphering nasopharyngeal carcinoma pathogenesis via proteomics
Published in Expert Review of Proteomics, 2019
Our lab first established a radioresistant subclone cell line (CNE2-IR) derived from NPC cell line CNE2 in 2010 to identify the proteins involved in radioresistance [88]. 2DE/MS analysis identified 34 differential proteins and validated that the downregulation of 14-3-3 sigma and maspin and the upregulation of GRP78 and Mn-SOD were significantly correlated with NPC radioresistance [88]. The same radioresistant subclone cell line was reused recently to detect a boarder coverage of radioresistance-related proteome using TMT labeling and LC–MS/MS [89]. A total of 5185 proteins were quantified, among which HSP27, SOD2, and PRDX1 with similar expression difference were also observed in the previous study [88]. Further functional study revealed MAPK15 as a novel potential regulator of radioresistance in NPC cells [89]. Another research group also established a radioresistant CNE-2R cell line and identified 16 differentially expressed proteins, including upregulation of Nm23 H1 and downregulation of NPM1 and annexin A3 in the radioresistant NPC cells [90,91]. The research group further analyzed the differential secretomes between the CNE-2R cells and the parental sensitive control, resulted in a collection of secretory proteins including increased cofilin-2 and CD166 and decreased sulfhydryl oxidase 1 and fibrillin-2, that might be relevant to the radioresistance in NPC cells [92]. Based on the proteomic analysis of radioresistant NPC tissues and radiosensitive NPC tissues, 12 proteins were identified aberrantly expressed, and ERp29 was validated to associate with radioresistance in NPC [93]. Another radioresistant NPC cell line CNE1-IR was established in a study, and comparative proteomics found overexpression of HSP27 to be involved in the NPC radioresistance [94]. Of note, HSP27 was consistently identified upregulated in the radioresistant NPC subclone cells or tissues in the aforementioned studies [88,89,93], which indicated that HSP27 might be a potential therapeutic target and of value in the assessment therapeutic efficacy in the treatment of NPC.