Protein Kinases: Key Players in Carcinogenesis

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 654

Special Issue Editor

Department of Cell Biology, Tongji University School of Medicine, Shanghai 200331, China
Interests: cellular and molecular mechanism; active ingredients of natural products; proteases and protein kinases

Special Issue Information

Dear Colleagues,

As we know, protein kinases play pivotal roles in numerous cellular processes, including cell proliferation, differentiation, and apoptosis, and their deregulation can contribute to the initiation and progression of cancer. This Special Issue explores the intricate relationship between protein kinases and carcinogenesis, providing a comprehensive overview of current advancements, challenges, and future directions in this exciting field.

The focus of this Special Issue encompasses the molecular mechanisms underlying the deregulation of protein kinases in cancer cells, as well as the downstream signaling pathways that are activated or inhibited as a result. We invite submissions that investigate the roles of protein kinases in promoting cell proliferation and survival, cancer invasion and metastasis, and the development of therapeutic strategies targeting protein kinases in cancer treatment.

Of particular interest are studies that investigate the efficacy and mechanisms of action of kinase inhibitors, which have shown promising results in clinical trials, as well as their potential for combination therapies with other anticancer agents. Additionally, we encourage submissions that explore the roles of protein kinases in cancer stem cells, which are thought to be responsible for cancer recurrence and resistance to therapy.

By bringing together a diverse range of perspectives and approaches, this Special Issue aims to foster new collaborations and stimulate further research in the field of protein kinase research in carcinogenesis. We invite researchers from around the world to share their latest findings and insights, and we look forward to presenting a stimulating and informative Special Issue that will benefit the entire scientific community.

Dr. Yingyu Cui
Guest Editor

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Keywords

  • protein kinases
  • carcinogenesis
  • molecular mechanisms
  • kinase inhibitors
  • cancer stem cells

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Published Papers (1 paper)

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Research

24 pages, 7124 KiB  
Article
In Silico Discovery of a Novel Potential Allosteric PI3Kα Inhibitor Incorporating 3-(2-Chloro-5-fluorophenyl)isoindolin-1-one to Target Head and Neck Squamous Cell Carcinoma
by Wenqing Jia and Xianchao Cheng
Biology 2025, 14(7), 896; https://doi.org/10.3390/biology14070896 - 21 Jul 2025
Viewed by 392
Abstract
Phosphatidylinositol 3-kinase alpha (PI3Kα) is frequently mutated in head and neck squamous cell carcinoma (HNSCC), leading to the constitutive activation of the PI3K/Akt pathway, which promotes tumor cell proliferation, survival, and metastasis. PI3Kα allosteric inhibitors demonstrate therapeutic potential as both monotherapy and combination [...] Read more.
Phosphatidylinositol 3-kinase alpha (PI3Kα) is frequently mutated in head and neck squamous cell carcinoma (HNSCC), leading to the constitutive activation of the PI3K/Akt pathway, which promotes tumor cell proliferation, survival, and metastasis. PI3Kα allosteric inhibitors demonstrate therapeutic potential as both monotherapy and combination therapy, particularly in patients with PIK3CA mutations or resistance to immunotherapy, through the precise targeting of mutant PI3Kα. Compared to ATP-competitive PI3Kα inhibitors such as Alpelisib, the allosteric inhibitor RLY-2608 exhibits enhanced selectivity for mutant PI3Kα while minimizing the inhibition of wild-type PI3Kα, thereby reducing side effects such as hyperglycemia. To date, no allosteric PI3Kα inhibitors have been approved for clinical use. To develop novel PI3Kα inhibitors with improved safety and efficacy, we employed a scaffold hopping approach to structurally modify RLY-2608 and constructed a compound library. Based on the structural information of the PI3Kα allosteric site, we conducted the systematic virtual screening of 11,550 molecules from databases to identify lead compounds. Through integrated approaches, including molecular docking studies, target validation, druggability evaluation, molecular dynamics simulations, and metabolic pathway and metabolite analyses, we successfully identified a promising novel allosteric PI3Kα inhibitor, H-18 (3-(2-chloro-5-fluorophenyl)isoindolin-1-one). H-18 has not been previously reported as a PI3Kα inhibitor, and provides an excellent foundation for subsequent lead optimization, offering a significant starting point for the development of more potent PI3Kα allosteric inhibitors. Full article
(This article belongs to the Special Issue Protein Kinases: Key Players in Carcinogenesis)
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