Protein Kinases in Cancer: From Carcinogenesis to Therapy and Resistance
Year: 2026
Type: article
Abstract: Protein kinases regulate proliferation, genome maintenance, cellular plasticity, metabolism, and replicative potential. Their effects in cancer depend on genotype, tissue, cell state, and treatment history, which complicates both functional classification and therapeutic targeting. This narrative review connects these biological contexts to treatment dependencies. It distinguishes protein kinases from related lipid kinases, phosphatases, and pseudokinase scaffolds, and organizes the mechanistic discussion around interconnected functional axes. Particular attention is given to cell-cycle checkpoints and DNA-damage responses, through which genome-protective functions can become survival dependencies in established tumors. The therapeutic discussion distinguishes oncogenic-driver inhibition, suppression of adaptive signaling, and exploitation of conditional or synthetic-lethal vulnerabilities. Genotype-specific drug responses, tissue-dependent feedback, and clinical trial results illustrate how biomarkers and prior therapy influence treatment selection. Resistance is examined in relation to treatment timing, molecular reassessment, and the distinction between target alterations, bypass signaling, and histological transformation. Emerging degradation and delivery strategies are considered alongside pharmacological exposure, normal-tissue toxicity, and the limitations of preclinical and early clinical evidence. The resulting framework links kinase mechanism to biomarker, therapeutic strategy, and resistance. Further progress requires the functional validation of proposed dependencies, prospective evaluation of patient-selection methods, and treatment schedules that maintain a tolerable therapeutic window.
Source: Biology
Authors: Jiao Feng, Zhaoxuan Wang, Ying-Yu Cui
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7225782753