Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer

Leire Arrizabalaga; Esmeralda García-Torralba; Lorenzo Galluzzi; Aitziber Buqué

doi:10.1016/j.molmed.2024.12.009

Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer

Leire Arrizabalaga, Esmeralda García-Torralba, Lorenzo Galluzzi, Aitziber Buqué

Fox Chase Cancer Center

Research output: Contribution to journal › Article › peer-review

Abstract

Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR+ breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.

Original language	English
Pages (from-to)	495-497
Number of pages	3
Journal	Trends in Molecular Medicine
Volume	31
Issue number	6
Early online date	Nov 27 2024
DOIs	https://doi.org/10.1016/j.molmed.2024.12.009
State	Published - Jun 2025

Keywords

RB1
type I interferon
DREAM complex
MDM2
immune checkpoint inhibitors
non-oncogene addiction
Humans
Cellular Senescence/drug effects
Antineoplastic Agents/therapeutic use
Drug Resistance, Neoplasm/drug effects
Tumor Suppressor Protein p53/metabolism
Cyclin-Dependent Kinase 2/antagonists & inhibitors
Animals
Protein Kinase Inhibitors/therapeutic use
Female
Breast Neoplasms/drug therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molmed.2024.12.009

Cite this

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title = "Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer",

abstract = "Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR+ breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.",

keywords = "RB1, type I interferon, DREAM complex, MDM2, immune checkpoint inhibitors, non-oncogene addiction, Humans, Cellular Senescence/drug effects, Antineoplastic Agents/therapeutic use, Drug Resistance, Neoplasm/drug effects, Tumor Suppressor Protein p53/metabolism, Cyclin-Dependent Kinase 2/antagonists & inhibitors, Animals, Protein Kinase Inhibitors/therapeutic use, Female, Breast Neoplasms/drug therapy",

author = "Leire Arrizabalaga and Esmeralda Garc{\'i}a-Torralba and Lorenzo Galluzzi and Aitziber Buqu{\'e}",

year = "2025",

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doi = "10.1016/j.molmed.2024.12.009",

language = "English",

volume = "31",

pages = "495--497",

journal = "Trends in Molecular Medicine",

issn = "1471-4914",

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TY - JOUR

T1 - Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer

AU - Arrizabalaga, Leire

AU - García-Torralba, Esmeralda

AU - Galluzzi, Lorenzo

AU - Buqué, Aitziber

PY - 2025/6

Y1 - 2025/6

N2 - Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR+ breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.

AB - Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR+ breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.

KW - RB1

KW - type I interferon

KW - DREAM complex

KW - MDM2

KW - immune checkpoint inhibitors

KW - non-oncogene addiction

KW - Humans

KW - Cellular Senescence/drug effects

KW - Antineoplastic Agents/therapeutic use

KW - Drug Resistance, Neoplasm/drug effects

KW - Tumor Suppressor Protein p53/metabolism

KW - Cyclin-Dependent Kinase 2/antagonists & inhibitors

KW - Animals

KW - Protein Kinase Inhibitors/therapeutic use

KW - Female

KW - Breast Neoplasms/drug therapy

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DO - 10.1016/j.molmed.2024.12.009

M3 - Article

C2 - 39732571

SN - 1471-4914

VL - 31

SP - 495

EP - 497

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 6

ER -

Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer

Abstract

Keywords

UN SDGs

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