scholarly journals Challenges in validating candidate therapeutic targets in cancer

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jeffrey Settleman ◽  
Charles L Sawyers ◽  
Tony Hunter
Keyword(s):  
Cancer Research ◽  
Protein Kinase ◽  
Therapeutic Target ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Compelling Evidence ◽  
Attractive Therapeutic Target ◽  
Research Tools

More than 30 published articles have suggested that a protein kinase called MELK is an attractive therapeutic target in human cancer, but three recent reports describe compelling evidence that it is not. These reports highlight the caveats associated with some of the research tools that are commonly used to validate candidate therapeutic targets in cancer research.

scholarly journals Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 115 ◽  
Author(s):  
Jack Prescott ◽  
Simon Cook
Keyword(s):  
Drug Discovery ◽  
Protein Kinase ◽  
Drug Development ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Clinical Success ◽  
Alternative Strategies ◽  
Challenges And Opportunities ◽  
Attractive Therapeutic Target ◽  
Clinical Models

Deregulated NF-κB signalling is implicated in the pathogenesis of numerous human inflammatory disorders and malignancies. Consequently, the NF-κB pathway has attracted attention as an attractive therapeutic target for drug discovery. As the primary, druggable mediator of canonical NF-κB signalling the IKKβ protein kinase has been the historical focus of drug development pipelines. Thousands of compounds with activity against IKKβ have been characterised, with many demonstrating promising efficacy in pre-clinical models of cancer and inflammatory disease. However, severe on-target toxicities and other safety concerns associated with systemic IKKβ inhibition have thus far prevented the clinical approval of any IKKβ inhibitors. This review will discuss the potential reasons for the lack of clinical success of IKKβ inhibitors to date, the challenges associated with their therapeutic use, realistic opportunities for their future utilisation, and the alternative strategies to inhibit NF-κB signalling that may overcome some of the limitations associated with IKKβ inhibition.

AMPK as a New Attractive Therapeutic Target for Disease Prevention: The Role of Dietary Compounds AMPK and Disease Prevention

2016 ◽  
Vol 17 (8) ◽  
pp. 865-889 ◽  
Author(s):  
Massimiliano Gasparrini ◽  
Francesca Giampieri ◽  
Josè M. Alvarez Suarez ◽  
Luca Mazzoni ◽  
Tamara Y. Forbes Hernandez ◽  
...  
Keyword(s):  
Disease Prevention ◽  
Therapeutic Target ◽  
Attractive Therapeutic Target

Protein Kinase C – Possible Therapeutic Target to Treat Cardiovascular Diseases

2010 ◽  
Vol 10 (4) ◽  
pp. 292-308 ◽  
Author(s):  
Yamini S. Bynagari-Settipalli ◽  
Ramya Chari ◽  
Laurie Kilpatrick ◽  
Satya P. Kunapuli
Keyword(s):  
Protein Kinase C ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Therapeutic Target ◽  
Kinase C

scholarly journals Crk and CrkL as Therapeutic Targets for Cancer Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 739
Author(s):  
Taeju Park
Keyword(s):  
Tumor Cell ◽  
Cancer Treatment ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Viral Oncoprotein ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs ◽  
Cell Functions

Crk and CrkL are cellular counterparts of the viral oncoprotein v-Crk. Crk and CrkL are overexpressed in many types of human cancer, correlating with poor prognosis. Furthermore, gene knockdown and knockout of Crk and CrkL in tumor cell lines suppress tumor cell functions, including cell proliferation, transformation, migration, invasion, epithelial-mesenchymal transition, resistance to chemotherapy drugs, and in vivo tumor growth and metastasis. Conversely, overexpression of tumor cells with Crk or CrkL enhances tumor cell functions. Therefore, Crk and CrkL have been proposed as therapeutic targets for cancer treatment. However, it is unclear whether Crk and CrkL make distinct or overlapping contributions to tumor cell functions in various cancer types because Crk or CrkL have been examined independently in most studies. Two recent studies using colorectal cancer and glioblastoma cells clearly demonstrated that Crk and CrkL need to be ablated individually and combined to understand distinct and overlapping roles of the two proteins in cancer. A comprehensive understanding of individual and overlapping roles of Crk and CrkL in tumor cell functions is necessary to develop effective therapeutic strategies. This review systematically discusses crucial functions of Crk and CrkL in tumor cell functions and provides new perspectives on targeting Crk and CrkL in cancer therapy.

scholarly journals New insights on CRISPR/Cas9-based therapy for breast Cancer

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Hussein Sabit ◽  
Shaimaa Abdel-Ghany ◽  
Huseyin Tombuloglu ◽  
Emre Cevik ◽  
Amany Alqosaibi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Animal Models ◽  
Human Cancer ◽  
Step Process ◽  
Cancer Initiation ◽  
Malignant State ◽  
Treat Breast Cancer

AbstractCRISPR/Cas9 has revolutionized genome-editing techniques in various biological fields including human cancer research. Cancer is a multi-step process that encompasses the accumulation of mutations that result in the hallmark of the malignant state. The goal of cancer research is to identify these mutations and correlate them with the underlying tumorigenic process. Using CRISPR/Cas9 tool, specific mutations responsible for cancer initiation and/or progression could be corrected at least in animal models as a first step towards translational applications. In the present article, we review various novel strategies that employed CRISPR/Cas9 to treat breast cancer in both in vitro and in vivo systems.

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