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RhoGTPases - A novel link between cytoskeleton organization and cisplatin resistance

Daphna Mokady1, David Meiri2

  • 1Princess Margaret Cancer Center, University Health Network, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada M5G 1L7.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|February 10, 2015
PubMed

Insights

Platinum compounds are vital cancer treatments, but cisplatin resistance hinders efficacy. Understanding Rho GTPases

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Platinum compounds, including cisplatin, are primary treatments for numerous solid tumors.
  • Cisplatin resistance significantly impedes effective cancer therapy.
  • Rho GTPases are critical regulators of cellular processes and implicated in cancer progression.

Purpose of the Study:

  • To review the role of the Rho subfamily of small GTPases in cancer.
  • To focus on the involvement of Rho GTPases in intrinsic and acquired cisplatin resistance.

Main Methods:

  • Literature review of studies investigating Rho GTPases in cancer and drug resistance.
  • Analysis of the regulatory mechanisms (GEFs, GAPs, GDIs) controlling Rho GTPase activity.
  • Examination of the distinct roles of RhoA, RhoB, and RhoC in cancer progression and chemoresistance.

Main Results:

  • Rho GTPases are molecular switches crucial for actin cytoskeleton organization and cellular functions like adhesion, trafficking, proliferation, and survival.
  • RhoA and RhoC are frequently upregulated in tumors, promoting transformation.
  • RhoB exhibits tumor suppressor characteristics, mediating proapoptotic effects.

Conclusions:

  • The Rho subfamily of proteins plays a multifaceted role in cancer development and progression.
  • Understanding the specific contributions of RhoA, RhoB, and RhoC to chemoresistance is essential for developing novel therapeutic strategies.
  • Targeting Rho GTPase pathways may offer new avenues to overcome cisplatin resistance in cancer treatment.
Keywords:
Cancer therapyChemoresistanceCisplatinCytoskeletonDrug resistanceRhoARhoGTPasesRock

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