Luqman Saheed1* and Ali Abdullahi Damasak2
1Department of Biochemistry, Faculty of Life Sciences, University of Maiduguri, Nigeria.
2Department of Nutrition and Dietetics, Faculty of Basic Medical Sciences, University of Maiduguri, Nigeria
*Corresponding author’s Email: shaokarneey@gmail.com, doi.org/10.55639/607.020100157
ABSTRACT
Protein kinases are central regulators of cellular communication and control processes including proliferation, differentiation, metabolism, survival, migration, DNA-damage responses and immune function. Their abnormal activation or expression contributes to the development and progression of many cancers through mutations, gene amplification, chromosomal rearrangements, altered expression and disruption of regulatory networks. Because cancer cells may become highly dependent on aberrant kinase signalling, protein kinases have become important targets for precision cancer therapy. The clinical development of kinase inhibitors has produced substantial benefits in several malignancies, particularly those driven by actionable molecular alterations. However, the initial effectiveness of these therapies is frequently followed by disease progression as tumor cells adapt to treatment. Drug resistance may result from secondary mutations in the target kinase, activation of bypass pathways, downstream signalling reactivation, tumor heterogeneity, phenotypic and epigenetic adaptation, altered drug transport, metabolic reprogramming and protective interactions with the tumor microenvironment. This review examines the structural and biological characteristics of protein kinases and their contribution to cancer development and progression. It further discusses major mechanisms responsible for resistance to kinase-targeted therapy and evaluates current approaches for overcoming resistance, including next-generation inhibitors, rational combination therapy, allosteric and covalent inhibition, biomarker-guided treatment, liquid biopsy, adaptive treatment, tumor-agnostic therapy and targeted protein degradation. Emerging applications of computational drug discovery and multi-omics approaches are also considered. A clearer understanding of kinase signalling and tumor evolution may support more durable treatment strategies and help move precision oncology toward earlier prediction and prevention of therapeutic resistance.
KEYWORDS
Oncogenic
signalling,
Phosphorylation,
Kinase
inhibitors,
Therapeutic
resistance.