A comprehensive new review highlights the growing importance of FOXK2, a versatile transcription factor, in shaping cancer behavior and influencing clinical outcomes across a wide range of tumor types. The article brings together emerging knowledge to clarify how this gene functions in cancer and why it is attracting increasing attention as a potential diagnostic and prognostic marker.
FOXK2 is shown to play a central role in regulating essential cellular processes, including metabolism, DNA maintenance, and cell survival. Its activity is now recognized as highly dynamic in cancer, where it can act either as an oncogene or a tumor suppressor, depending on the biological context. This duality positions FOXK2 as a critical factor in understanding how tumors grow, adapt, and respond to treatment.
The review emphasizes that gene expression patterns of FOXK2 vary significantly across cancers. Elevated levels are frequently observed in multiple tumor types, including liver, lung, breast, and colorectal cancers, suggesting a broad involvement in tumor development. In contrast, reduced expression in certain cancers highlights a complex and context-dependent role.
Importantly, FOXK2 is closely linked to cellular stress responses, particularly those associated with DNA damage. Its increased activity in tumor cells may reflect an adaptive mechanism that helps cancer cells survive under conditions of genomic instability. This connection underscores its relevance in disease progression and therapeutic resistance.
The article also explores how FOXK2 contributes to patient outcomes. In some cancers, higher expression levels are associated with less favorable survival, while in others, reduced expression may signal poorer prognosis. These contrasting patterns reinforce the need for a more nuanced understanding of FOXK2 in different disease settings.
Beyond expression levels, the review highlights multiple layers of gene regulation, including methylation, copy number variations, and post-transcriptional modifications. Among these, copy number changes emerge as a particularly influential factor in driving FOXK2 activity across cancers.
Collectively, these findings position FOXK2 as a promising target for future clinical applications. Its ability to reflect tumor biology and influence disease behavior suggests potential use in precision medicine, where it could help guide diagnosis, predict outcomes, and inform treatment strategies.
As understanding of FOXK2 continues to evolve, this synthesis of current knowledge underscores its growing significance in cancer research and its potential to shape the next generation of clinical innovations.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Renata Ivo Vasconcelos, Luciana da Torre Carneiro, Raquel Ciuvalschi Maia, Thaís Hancio, Gabriela Nestal de Moraes, FOXK2 gene expression in cancer: Potential regulatory mechanisms and clinical implications, Genes & Diseases, Volume 13, Issue 4, 2026, 101951, https://doi.org/10.1016/j.gendis.2025.101951

Funding
L’Oreál-UNESCO-ABC For Women in Science, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro SEI-26003/004812/202
L’Oreál-UNESCO-ABC For Women in Science, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro SEI-260003/001554/2022
National Council for Scientific and Technological Development 307427/2022-6
National Council for Scientific and Technological Development 408314/2021-4
CNPq fellowships
FAPERJ 260003/007036/2022
CNPq-INCT program 408340/2024-0