Related Experiment Video

Updated: Jul 6, 2025

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression
11:02

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Published on: August 3, 2011

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A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer

Niki Tzenaki1, Lydia Xenou1, Evangelia Goulielmaki1

  • 1Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece.

Communications Biology
|January 5, 2024
PubMed

Insights

Targeting RhoA and p110δ PI3K simultaneously blocks melanoma and SCC skin cancer growth and metastasis. This novel combination therapy shows efficacy regardless of BRAF mutation status, offering new hope for skin cancer treatment.

Area of Science:

  • Oncology
  • Dermatology
  • Cancer Biology

Background:

  • Malignant melanoma and squamous cell carcinoma (SCC) are aggressive skin cancers with increasing incidence and limited treatment options.
  • Targeting key molecular pathways is crucial for effective cancer therapy.

Purpose of the Study:

  • To investigate the efficacy of a combined therapeutic strategy targeting RhoA and p110δ PI3K in blocking melanoma and SCC development and metastasis.
  • To explore the underlying mechanisms and potential biomarkers associated with this combined treatment.

Main Methods:

  • Induction of RhoA activity in tumor cells by deleting p190RhoGAP.
  • Adoptive transfer of macrophages from δD910A/D910A mice into tumor-bearing mice.
  • Assessment of tumor growth, metastasis, and molecular markers including ATX and RhoA activity.
  • Evaluation of treatment efficacy in tumors with and without BRAF mutations.

Main Results:

  • Combined targeting of RhoA and p110δ PI3K abrogated the growth and progression of melanoma and SCC tumors.
  • The treatment's efficacy was consistent across tumors with and without the BRAF(V600E) mutation.
  • This combinatorial approach led to decreased lysophosphatidic acid (LPA) signaling, evidenced by reduced autotaxin (ATX) expression, bypassing feedback loops.

Conclusions:

  • Simultaneous targeting of cancer cells (via RhoA induction) and macrophages (via p110δ PI3K inhibition) is a promising strategy for skin cancer therapy.
  • A reverse link between autotaxin (ATX) and RhoA was identified.
  • p110δ PI3K inhibition represents a beneficial combinatorial regimen for treating skin cancers, including melanoma and SCC.

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