Yadav Suresh Singh, Kalia Punita, Kaur Navneet, Sharma Sourav, Thakur Shambhavi, Kumari Soni, Nair Rohini Ravindran
Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Department of Medical Biotechnology, Gujarat Biotechnology University, Gandhinagar, Gujarat, 382355, India.
Discov Oncol. 2025 Sep 22;16(1):1690. doi: 10.1007/s12672-025-02261-4.
Chemoresistance is a major obstacle in cancer treatment, and it often results in treatment failure and disease progression. Among the plethora of factors contributing to chemoresistance, the transcription factor Krüppel-like factor 4 (KLF4) has emerged as a pivotal player. This review discusses the role of KLF4 in orchestrating various mechanisms underlying cancer chemoresistance. KLF4, originally identified as a regulator of cell differentiation and proliferation, has recently gained attention for its role in modulating cellular responses to chemotherapeutic agents. Through complex regulatory networks, KLF4 modulates the process of drug efflux, DNA repair, apoptotic signaling, tumor heterogeneity, and cancer cell stemness, leading to the development of cancer chemoresistance. Additionally, tissue or cell types specific post-translational modification (PTM) of KLF4 plays a significant role in the development of cancer chemoresistance. The review explores emerging possibilities and available information that can be utilised to understand the mechanism of chemoresistance mediated by KLF4 in cancer. In conclusion, understanding the complex mechanisms through which KLF4 orchestrates cancer chemoresistance opens promising avenues for developing more effective therapeutic interventions to combat treatment-resistant cancers.
