Kinesin superfamily proteins in cancer: unveiling their role in chemotherapy.

Kinesin superfamily proteins (KIFs) are driver proteins used by microtubules for intracellular transport, cellular homeostasis, and mitosis. Reportedly, the aberration in the expression of these proteins has been found to mediate sensitivity to chemotherapy. KIF5A, KIF11, and KIF20A are consistently involved in resistance to paclitaxel and docetaxel in breast, lung, and prostate cancers, while KIF14 overexpression is a prognostic marker for poor outcomes in paclitaxel-treated triple-negative breast and cervical cancer. KIF14 and KIF23 in HCC enhance sorafenib and cisplatin resistance, while suppression of KIF5B or KIF20A increases sensitivity to oxaliplatin in colorectal cancer. Clinic-applied fusions of KIF5B with ALK or EGFR have made it possible to use targeted therapy in non-small cell lung cancer. From a mechanistic point of view, PI3K/Akt, JAK/STAT, and NF-κB activation, metabolic reprogramming, and inhibition of cellular programmed death are involved in KIF-mediated resistance. KIF3A or KIF11 silencing increases chemosensitivity, suggesting a dual role here. Present approaches-small-molecule inhibitors, microRNA modulation, and KIF20A peptide vaccines-are hopeful but are beset by issues of toxicity and specificity. Overall, KIFs are context-dependent regulators of chemoresistance and are multifunctional but promising precision oncology targets.