All screens lead to polo-like kinase 1: A central node in cancer therapeutics and resistance
Abstract
A C TPolo-like kinase 1 (PLK1) is a mitotic kinase that is frequently overexpressed across many cancer types and strongly associated with poor prognosis and resistance to treatment. Comprehensive genomic, genetic, and pharmacological screens consistently pinpoint PLK1 as a therapeutic target in oncology. Despite promising preclinical anti-tumor efficacy of PLK1 inhibitors, clinical outcome as a monotherapy has been modest, necessitating the development of next-generation PLK1 inhibitors and combination strategies. The role of PLK1 extends beyond cell cycle regulation to tumor progression, immune evasion, and the tumor microenvironment. Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo-and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment.
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BibTeX
@article{alsouhibani2026screens,
title = {{All screens lead to polo-like kinase 1: A central node in cancer therapeutics and resistance}},
author = {Norah Al-Souhibani and Otilia Menyhart and Maeva Dufies and Abdul K Siraj and Pratheesh K Poyil and Edward Hitti and Khawla Al-Kuraya and Balázs Győrffy and Pagès Gilles and Khalid S A Khabar},
journal = {Pharmacological Research},
year = {2026},
month = may,
doi = {10.1016/j.phrs.2026.108252},
url = {https://hal.science/hal-05798880v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - All screens lead to polo-like kinase 1: A central node in cancer therapeutics and resistance
AU - Norah Al-Souhibani
AU - Otilia Menyhart
AU - Maeva Dufies
AU - Abdul K Siraj
AU - Pratheesh K Poyil
AU - Edward Hitti
AU - Khawla Al-Kuraya
AU - Balázs Győrffy
AU - Pagès Gilles
AU - Khalid S A Khabar
PY - 2026
DA - 2026/05/18
JO - Pharmacological Research
DO - 10.1016/j.phrs.2026.108252
UR - https://hal.science/hal-05798880v1
AB - A C TPolo-like kinase 1 (PLK1) is a mitotic kinase that is frequently overexpressed across many cancer types and strongly associated with poor prognosis and resistance to treatment. Comprehensive genomic, genetic, and pharmacological screens consistently pinpoint PLK1 as a therapeutic target in oncology. Despite promising preclinical anti-tumor efficacy of PLK1 inhibitors, clinical outcome as a monotherapy has been modest, necessitating the development of next-generation PLK1 inhibitors and combination strategies. The role of PLK1 extends beyond cell cycle regulation to tumor progression, immune evasion, and the tumor microenvironment. Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo-and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment.
SN - 1043-6618
SN - 1096-1186
ER -