Kinase Signaling and Kinase-Targeted Therapies on Cancer: Advances, Challenges, and Future Directions—Second Edition

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 2275

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Istituto di Endocrinologia e Oncologia Sperimentale del CNR, Dipartimento di Medicina Molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
Interests: cancer; kinase inhibitor; target therapy; signal transduction; cell cycle; mitogenesis; survival; resistance
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Special Issue Information

Dear Colleagues,

The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Transferring γ-phosphate onto diverse substrates enables kinases to regulate key cellular functions. As many human diseases result from the mutation and overexpression of kinases, targeting this enzyme class symbolizes an important strategy for drug development. Many of these kinases are associated with human cancer initiation and progression. The recent development of small molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Kinase inhibitors represent a targeted therapy resulting from the understanding of molecular genetics and molecular signaling pathways. This class of therapeutics represents a transformation from conventional chemotherapy to targeted cancer treatment. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, the tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. Due to the clinical importance of kinase inhibitors, multiple strategies are required to overcome resistance mechanisms and develop more effective targeted therapies. Moreover, kinase inhibitors are not only important for the treatment of cancer but also help us better understand the physiological roles of kinases. This Special Issue intends to serve as a compilation overviewing kinase signaling and kinase-targeted drug discovery and development in relation to oncology and highlighting the challenges and future potential for kinase-targeted cancer therapies.

Prof. Dr. Valentina De Falco
Guest Editor

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Keywords

  • cancer
  • oncogene
  • kinase inhibitors
  • tumor drug resistance
  • signal transduction
  • survival
  • cell reprogramming
  • target therapy
  • cancer heterogeneity
  • biomarkers

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Review

22 pages, 13640 KiB  
Review
Unraveling the Mystery of Energy-Sensing Enzymes and Signaling Pathways in Tumorigenesis and Their Potential as Therapeutic Targets for Cancer
by Zeenat Mirza and Sajjad Karim
Cells 2024, 13(17), 1474; https://doi.org/10.3390/cells13171474 - 2 Sep 2024
Viewed by 1364
Abstract
Cancer research has advanced tremendously with the identification of causative genes, proteins, and signaling pathways. Numerous antitumor drugs have been designed and screened for cancer therapeutics; however, designing target-specific drugs for malignant cells with minimal side effects is challenging. Recently, energy-sensing- and homeostasis-associated [...] Read more.
Cancer research has advanced tremendously with the identification of causative genes, proteins, and signaling pathways. Numerous antitumor drugs have been designed and screened for cancer therapeutics; however, designing target-specific drugs for malignant cells with minimal side effects is challenging. Recently, energy-sensing- and homeostasis-associated molecules and signaling pathways playing a role in proliferation, apoptosis, autophagy, and angiogenesis have received increasing attention. Energy-metabolism-based studies have shown the contribution of energetics to cancer development, where tumor cells show increased glycolytic activity and decreased oxidative phosphorylation (the Warburg effect) in order to obtain the required additional energy for rapid division. The role of energy homeostasis in the survival of normal as well as malignant cells is critical; therefore, fuel intake and expenditure must be balanced within acceptable limits. Thus, energy-sensing enzymes detecting the disruption of glycolysis, AMP, ATP, or GTP levels are promising anticancer therapeutic targets. Here, we review the common energy mediators and energy sensors and their metabolic properties, mechanisms, and associated signaling pathways involved in carcinogenesis, and explore the possibility of identifying drugs for inhibiting the energy metabolism of tumor cells. Furthermore, to corroborate our hypothesis, we performed meta-analysis based on transcriptomic profiling to search for energy-associated biomarkers and canonical pathways. Full article
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