Related Experiment Video

Updated: Oct 5, 2025

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay
09:03

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay

Published on: June 30, 2023

1.2K

Endothelial p130cas confers resistance to anti-angiogenesis therapy

Yunfei Wen1, Anca Chelariu-Raicu1, Sujanitha Umamaheswaran1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Boulevard, Houston, TX 77030, USA.

Cell Reports
|January 26, 2022
PubMed

Insights

Overcoming resistance to anti-VEGF antibodies (AVAs) in ovarian cancer is crucial. Targeting endothelial p130cas and blocking autophagy offers a promising strategy to re-sensitize tumors to AVA therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Anti-angiogenic therapies, including anti-VEGF antibodies (AVAs), are used for cancer treatment.
  • Adaptive resistance frequently limits the efficacy of AVAs.
  • Understanding resistance mechanisms is vital for improving cancer therapy.

Purpose of the Study:

  • To investigate the mechanisms of adaptive resistance to AVAs in ovarian cancer.
  • To identify novel therapeutic targets for overcoming AVA resistance.

Main Methods:

  • Orthotopic ovarian cancer models with AVA-adaptive resistance were utilized.
  • Genomic profiling of resistant tumors was performed.
  • Endothelial cell death pathways and autophagy were analyzed.
  • Targeting of p130cas using nanoparticles and genetic ablation was tested.

Main Results:

  • Endothelial p130cas was identified as a key factor in AVA resistance.
  • Bevacizumab treatment led to VEGFR2 cleavage and nuclear/autophagosomal internalization.
  • Nuclear VEGFR2 and p130cas fragments initiated endothelial cell death.
  • Blocking autophagy or targeting p130cas extended survival in resistant ovarian cancer models.
  • Elevated vascular p130cas correlated with poorer patient survival.

Conclusions:

  • Endothelial p130cas and VEGFR2 processing are critical in AVA resistance.
  • Strategies targeting p130cas and modulating autophagy can overcome AVA resistance.
  • Vascular p130cas is a potential prognostic biomarker for ovarian cancer.
Keywords:
TNKS1BP1VEGFR2adaptive resistanceangiogenesisanti-angiogenic therapyautophagyp130cas

More Related Videos

Isolation and Culture Expansion of Tumor-specific Endothelial Cells10:15

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Published on: October 14, 2015

11.4K
In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.0K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.0K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
238
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K