Role of Protein Post-Translational Modifications in Cancer: Mechanisms and Therapeutic Opportunities

A special issue of Kinases and Phosphatases (ISSN 2813-3757).

Deadline for manuscript submissions: 30 November 2025 | Viewed by 759

Special Issue Editors


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Guest Editor
Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan
Interests: the dysregulation of signal transduction; metabolic pathway in cancer progression; drug resistance
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Special Issue Information

Dear Colleagues,

Post-translational modifications (PTMs) represent a major biochemical mechanism for increasing the diversity of the proteome, allowing proteins to undergo functional changes that can be dynamically adjusted in response to both intracellular and extracellular signals. In cancer, PTMs such as phosphorylation, ubiquitination, acetylation, glycosylation, and methylation are not merely secondary modifications; rather, they influence virtually every hallmark of cancer. These and other modifications regulate key cellular functions such as cell cycle progression, apoptosis, DNA repair, immune responses, and metabolism. However, cancer cells frequently hijack PTMs, exploiting these mechanisms to promote uncontrolled growth, evade apoptosis, drive metastasis, and resist treatment.

The targeting of these aberrant PTM pathways presents a vast array of potential avenues for therapeutic intervention. One of the most well-known examples is the aberrant tyrosine kinase activity of the BCR-ABL fusion protein in chronic myeloid leukemia. Imatinib, a pioneering therapeutic agent that targets this hyperactive kinase and was specifically developed for this purpose, exemplifies how correcting PTM-driven dysregulation can result in effective cancer treatment, opening the door to a wide range of cancer treatments.

This Special Issue will collect the latest research on the pivotal roles of PTMs in the diverse stages and forms of cancer, with particular interest in mechanistic studies aimed at revealing how specific PTMs contribute to tumor initiation, progression, and metastasis. Furthermore, comprehensive reviews of current treatments targeting PTMs, which should examine the efficacy of existing therapies and highlight new therapeutic avenues, will be welcomed.

By collecting a broad spectrum of research, the aim is to provide a deeper understanding of the molecular mechanism controlled by PTMs in tumors and of how manipulating PTMs can revolutionize cancer treatment and improve patient outcomes.

You may choose our Joint Special Issue in IJMS.

Dr. Mauro Salvi
Prof. Dr. Wei-Chien Huang
Dr. Josefa León
Guest Editors

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Keywords

  • phosphorylation
  • acetylation
  • methylation
  • sumoylation
  • ubiquitination
  • glycosylation
  • acylation
  • signal transduction
  • inhibitors

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Published Papers (2 papers)

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Review

16 pages, 810 KiB  
Review
Bruton’s Tyrosine Kinase: A Double-Edged Sword in Cancer and Aging
by Zahraa Qusairy and Miran Rada
Kinases Phosphatases 2025, 3(2), 10; https://doi.org/10.3390/kinasesphosphatases3020010 - 7 May 2025
Viewed by 144
Abstract
Bruton’s tyrosine kinase (BTK) is a key signaling molecule involved in both hematological malignancies and solid tumors. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), BTK mediates B-cell receptor signaling, promoting tumor survival and proliferation, leading to the [...] Read more.
Bruton’s tyrosine kinase (BTK) is a key signaling molecule involved in both hematological malignancies and solid tumors. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), BTK mediates B-cell receptor signaling, promoting tumor survival and proliferation, leading to the development of BTK inhibitors like ibrutinib that improve patient outcomes. In solid tumors, BTK isoforms, particularly p65BTK, contribute to tumor growth and therapy resistance, with inhibition showing promise in cancers like colorectal, ovarian, and non-small cell lung cancer. BTK also influences the tumor microenvironment by modulating immune cells such as myeloid-derived suppressor cells and tumor-associated macrophages, aiding immune evasion. BTK inhibition can enhance anti-tumor immunity and reduce inflammation-driven tumor progression. Additionally, BTK contributes to tumor angiogenesis, with inhibitors like ibrutinib showing anti-angiogenic effects. Beyond cancer, BTK is linked to aging, where its modulation may reduce senescent cell accumulation and preserve cognitive function. This review explores BTK’s dual role, focusing on its oncogenic effects and potential impact on aging processes. We also discuss the use of BTK inhibitors in cancer treatment and their potential to address age-related concerns, providing a deeper understanding of BTK as a therapeutic target and mediator in the complex relationship between cancer and aging. Full article
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22 pages, 1184 KiB  
Review
Role of Histone Deacetylases in Drug-Resistant Melanoma: Mechanisms and Therapeutic Implications
by Bhuvanesh Sukhlal Kalal
Kinases Phosphatases 2025, 3(2), 8; https://doi.org/10.3390/kinasesphosphatases3020008 - 21 Apr 2025
Viewed by 283
Abstract
Melanoma, known for its aggressive nature and propensity for developing drug resistance, remains a significant clinical challenge. The emergence of resistance to both targeted therapies (like BRAF/MEK inhibitors) and immunotherapies is a major obstacle to achieving durable responses and improving patient survival. HDACs, [...] Read more.
Melanoma, known for its aggressive nature and propensity for developing drug resistance, remains a significant clinical challenge. The emergence of resistance to both targeted therapies (like BRAF/MEK inhibitors) and immunotherapies is a major obstacle to achieving durable responses and improving patient survival. HDACs, a class of epigenetic enzymes, modulate gene expression and chromatin structure by removing acetyl groups from histone and non-histone proteins. In melanoma, aberrant HDAC activity contributes to resistance through multiple mechanisms. HDACs influence key oncogenic signaling pathways frequently dysregulated in melanoma, such as the MAPK, PI3K/AKT, and WNT/β-catenin cascades. By altering the activity of these pathways, HDACs promote the survival and proliferation of melanoma cells even in the presence of therapy. Beyond their direct effects on tumor cells, HDACs also play a crucial role in shaping the tumor microenvironment. They can suppress anti-tumor immune responses by reducing immune cell infiltration, modulating cytokine production, and fostering an immunosuppressive milieu. This further contributes to resistance to immunotherapies. Given the central role of HDACs in these resistance mechanisms, HDAC inhibitors (HDACis) have emerged as potential therapeutic agents to restore drug sensitivity. HDACis can induce cell death, inhibit proliferation, and enhance immune responses in melanoma cells. Preclinical and clinical studies have explored the combination of HDACis with existing therapies to overcome resistance. While promising, the clinical application of HDACis is accompanied by challenges, including toxicity, the need for biomarkers to predict response, and the optimization of combination strategies. Ongoing research is dedicated to developing more selective and potent HDACis and to better understand how to effectively incorporate them into melanoma treatment regimens. This review provides a comprehensive overview of the multifaceted ways in which HDACs contribute to melanoma drug resistance and discusses the potential of HDAC-targeted therapies to improve patient outcomes. Full article
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