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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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The ARK side of the cell: Kinases, metabolism, and therapeutic potential in malignancies

Viviana Coliboro-Dannich1, Alejandro Farías1, Luis Espinoza-Francine1

  • 1Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.

Pharmacological Research
|December 4, 2025
PubMed

Insights

AMP-activated protein kinase (AMPK)-related kinases (ARKs) are vital for cellular energy and stress responses. This review explores ARKs

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Metabolic regulation

Background:

  • AMPK-related kinases (ARKs) are a family of serine/threonine kinases crucial for cellular energy homeostasis and stress response.
  • While AMPK is a well-known regulator, its paralogs (ARKs) also significantly modulate metabolic adaptation, signal transduction, and tumorigenesis.
  • ARKs are increasingly recognized for their central role in cancer cell physiology.

Purpose of the Study:

  • To provide a comprehensive overview of the human AMPK-related kinases (ARKs) family.
  • To detail ARKs' structural features, regulatory mechanisms, and activation pathways.
  • To categorize ARKs based on shared molecular mechanisms and tumorigenic roles in cancer.

Main Methods:

  • Literature review and synthesis of existing research on ARKs.
  • Categorization of ARKs based on molecular mechanisms and cancer-related functions.
  • Analysis of ARKs' involvement in metabolic adaptation and stress signaling.

Main Results:

  • ARKs are involved in diverse cellular processes, particularly energy metabolism and stress signaling.
  • The review categorizes ARKs, highlighting their complex and multifaceted roles in cancer.
  • ARKs represent an underappreciated layer of metabolic and stress regulation in disease.

Conclusions:

  • Understanding ARKs' functions in cancer and other diseases offers insights into cellular adaptation.
  • ARKs are emerging as significant, yet underexplored, contributors to tumor biology.
  • Knowledge of ARKs presents new opportunities for targeted cancer therapeutic strategies.
Keywords:
AMPK-related kinasesCancer metabolismCancer therapyHippo pathwayMTOR/Akt pathwayOncogenes and tumor suppressorsTGFβ/SMAD pathway

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