EpCAM x RNA polymerase II

Last update 08 May 2025

Basic Info

Related Targets

EpCAMRNA polymerase II

Drugs associated with EpCAM x RNA polymerase II

chiHEA125-Ama

Target

EpCAM x RNA polymerase II

Mechanism

EpCAM inhibitors [+1]

Active Org.

Heidelberg Pharma AG

Originator Org.

Heidelberg Pharma AG

Active Indication

Pancreatic Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with EpCAM x RNA polymerase II

100 Translational Medicine associated with EpCAM x RNA polymerase II

0 Patents (Medical) associated with EpCAM x RNA polymerase II

Literatures (Medical) associated with EpCAM x RNA polymerase II

30 Apr 2015·Nature

TP53 loss creates therapeutic vulnerability in colorectal cancer

Article

Author: Rodriguez-Aguayo, Cristian ; Liu, Yunhua ; Maru, Dipen M ; Wan, Guohui ; Pahl, Andreas ; Sood, Anil K ; Lu, Xiongbin ; Ellis, Lee M ; Han, Cecil ; Jiang, Dahai ; Anderl, Jan ; Zhang, Xinna ; Ivan, Cristina ; Lopez-Berestein, Gabriel ; He, Xiaoming ; Huang, Xingxu ; Rao, Pulivarthi H

TP53, a well-known tumour suppressor gene that encodes p53, is frequently inactivated by mutation or deletion in most human tumours. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment owing to the complexity of p53 signalling. Here we demonstrate that genomic deletion of TP53 frequently encompasses essential neighbouring genes, rendering cancer cells with hemizygous TP53 deletion vulnerable to further suppression of such genes. POLR2A is identified as such a gene that is almost always co-deleted with TP53 in human cancers. It encodes the largest and catalytic subunit of the RNA polymerase II complex, which is specifically inhibited by α-amanitin. Our analysis of The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases reveals that POLR2A expression levels are tightly correlated with its gene copy numbers in human colorectal cancer. Suppression of POLR2A with α-amanitin or small interfering RNAs selectively inhibits the proliferation, survival and tumorigenic potential of colorectal cancer cells with hemizygous TP53 loss in a p53-independent manner. Previous clinical applications of α-amanitin have been limited owing to its liver toxicity. However, we found that α-amanitin-based antibody-drug conjugates are highly effective therapeutic agents with reduced toxicity. Here we show that low doses of α-amanitin-conjugated anti-epithelial cell adhesion molecule (EpCAM) antibody lead to complete tumour regression in mouse models of human colorectal cancer with hemizygous deletion of POLR2A. We anticipate that inhibiting POLR2A will be a new therapeutic approach for human cancers containing such common genomic alterations.

PeerJQ3 · BIOLOGY

Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

Q3 · BIOLOGY

ArticleOA

Author: Zeng, Guohua ; He, Zihao ; Duan, Xiaolu

BackgroundProstate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method.MethodsDifferentially expressed genes (DEGs) were filtered out from theGSE103512dataset and subjected to the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein–protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The University of California Santa Cruz Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts.ResultsTotally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in “oxidation-reduction process” and “positive regulation of transcription from RNA polymerase II promoter”; KEGG pathway analysis enriched mostly in “metabolic pathways” and “protein digestion and absorption.” Kallikrein-related peptidase 3, cadherin 1 (CDH1), Kallikrein-related peptidase 2 (KLK2), forkhead box A1 (FOXA1), and epithelial cell adhesion molecule (EPCAM) were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant gene expression omnibus datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients.ConclusionsThis study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.

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