Implications of KRAS in Molecular Signaling Pathways in Oral Squamous Cell Carcinoma: Interplay with Autophagy, Apoptosis, and Oxidative Stress

Bianca Voicu Balasea¹, Alexandra Popa^2,*, Florentina Rus², Radu Radulescu², Melis Izet¹, Alexandra Ripszky^1,2,*
1 The Interdisciplinary Center for Dental Research and Development, “Carol Davila” University of Medicine and Pharmacy, 19-21 Jean Louis Calderon, Bucharest, Romania
2 Department of Biochemistry, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 17-23 Plevnei Street, Bucharest, Romania
* Corresponding Author: Alexandra Popa. Email: email ; Alexandra Ripszky. Email: email

BIOCELL https://doi.org/10.32604/biocell.2026.082448

Received 16 March 2026; Accepted 15 May 2026; Published online 29 May 2026

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Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy often diagnosed at advanced stages and associated with poor prognosis. This review aims to summarize the role of Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling in OSCC progression, with particular emphasis on its involvement in the regulation of autophagy, apoptosis, and oxidative stress. KRAS contributes to tumor progression despite the low frequency of activating mutations, primarily through increased KRAS expression associated with activation of downstream signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) and rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (RAF/MEK/ERK). Collectively, KRAS is involved in a complex regulatory network comprising apoptosis, autophagy, and oxidative stress, thereby influencing tumor cell survival and therapeutic resistance. Targeting these pathways may represent a promising strategy to restore apoptotic responses and overcome treatment resistance in OSCC.

Keywords

Oral squamous cell carcinoma; Kirsten rat sarcoma viral oncogene homolog (KRAS); reactive oxygen species; autophagy; apoptosis; PI3K/AKT/mTOR pathway; RAF/MEK/ERK pathway

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Implications of KRAS in Molecular Signaling Pathways in Oral Squamous Cell Carcinoma: Interplay with Autophagy, Apoptosis, and Oxidative Stress

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