GABAB receptor is a novel drug target for pancreatic cancer

Activating mutations in KRAS (KRAS*) are present in nearly all pancreatic ductal adenocarcinoma (PDAC) cases and critical for tumor maintenance. By using an inducible KRAS* PDAC mouse model, we identified a deubiquitinase USP21-driven resistance mechanism to anti-KRAS* therapy. USP21 promotes KRAS*-independent tumor growth via its regulation of MARK3-induced macropinocytosis, which serves to maintain intracellular amino acid levels for anabolic growth. The USP21-mediated KRAS* bypass, coupled with the frequent amplification of USP21 in human PDAC tumors, encourages the assessment of USP21 as a novel drug target as well as a potential parameter that may affect responsiveness to emergent anti-KRAS* therapy.

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The Protein Kinase, RSK2, A Novel Drug Target for Breast Cancer

10.21236/ada437856 ◽

2005 ◽

Author(s):

Deborah A. Lannigan

Keyword(s):

Breast Cancer ◽

Protein Kinase ◽

Drug Target ◽

Novel Drug

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Identification of Antineoplastic Targets with Systems Approaches, Using Resveratrol as an In-Depth Case Study

Current Pharmaceutical Design ◽

10.2174/1381612823666170710152918 ◽

2017 ◽

Vol 23 (32) ◽

pp. 4773-4793 ◽

Cited By ~ 5

Author(s):

Nivedita Singh ◽

Sherry Freiesleben ◽

Olaf Wolkenhauer ◽

Yogeshwer Shukla ◽

Shailendra K. Gupta

Keyword(s):

Drug Target ◽

Complex Disease ◽

Biological Targets ◽

Systems Approaches ◽

Anticancer Mechanism ◽

Genetic And Environmental Factors ◽

Key Steps ◽

Network Approaches ◽

Novel Drug

The identification and validation of novel drug–target combinations are key steps in the drug discovery processes. Cancer is a complex disease that involves several genetic and environmental factors. High-throughput omics technologies are now widely available, however the integration of multi-omics data to identify viable anticancer drug-target combinations, that allow for a better clinical outcome when considering the efficacy-toxicity spectrum, is challenging. This review article provides an overview of systems approaches which help to integrate a broad spectrum of technologies and data. We focus on network approaches and investigate anticancer mechanism and biological targets of resveratrol using reverse pharmacophore mapping as an in-depth case study. The results of this case study demonstrate the use of systems approaches for a better understanding of the behavior of small molecule inhibitors in receptor binding sites. The presented network analysis approach helps in formulating hypotheses and provides mechanistic insights of resveratrol in neoplastic transformations.

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A Systematic Study of Novel Drug Delivery Mechanisms and Treatment Strategies for Pancreatic Cancer

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102539 ◽

2021 ◽

pp. 102539

Author(s):

Umme Hani ◽

Riyaz Ali M. Osmani ◽

Ayesha Siddiqua ◽

Shadma Wahab ◽

Sadia Batool ◽

...

Keyword(s):

Drug Delivery ◽

Pancreatic Cancer ◽

Systematic Study ◽

Treatment Strategies ◽

Novel Drug

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Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

Scientific Reports ◽

10.1038/s41598-021-92701-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pusheng Quan ◽

Kai Wang ◽

Shi Yan ◽

Shirong Wen ◽

Chengqun Wei ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Drug Target ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Control Group ◽

Drug Candidates ◽

Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

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4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma Brucei

Microorganisms ◽

10.3390/microorganisms9040826 ◽

2021 ◽

Vol 9 (4) ◽

pp. 826

Author(s):

Dorien Mabille ◽

Camila Cardoso Santos ◽

Rik Hendrickx ◽

Mathieu Claes ◽

Peter Takac ◽

...

Keyword(s):

Mode Of Action ◽

Drug Target ◽

Drug Targets ◽

De Novo ◽

Treatment Options ◽

Adenosine Kinase ◽

Nucleoside Analogues ◽

Purine Salvage ◽

Interacting Protein ◽

Novel Drug

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.

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