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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

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Immune-Mediated and Hypoxia-Regulated Programs: Accomplices in Resistance to Anti-angiogenic Therapies

Diego O Croci1, Santiago P Mendez-Huergo2, Juan P Cerliani2

  • 1Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina. dcrocirusso@gmail.com.

Handbook of Experimental Pharmacology
|April 14, 2017
PubMed

Insights

Resistance to anti-angiogenic therapies involves compensatory pathways, not gene mutations. Understanding these hypoxia- and immune-mediated mechanisms, including galectins, is key to developing new cancer treatments.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Resistance to targeted cancer therapies often involves genetic mutations.
  • However, resistance to anti-angiogenic therapies, like vascular endothelial growth factor (VEGF) blockade, relies on compensatory pathways.
  • These pathways activate alternative pro-angiogenic mechanisms, bypassing the drug target.

Purpose of the Study:

  • To elucidate the hypoxia-regulated and immune-mediated mechanisms driving resistance to anti-angiogenic therapies.
  • To highlight the role of galectins and glycosylated ligands in this resistance.
  • To explore strategies for overcoming compensatory angiogenesis and discuss combinatorial treatments.

Main Methods:

  • Review and synthesis of current literature on resistance to anti-angiogenic therapies.
  • Focus on cellular and molecular mechanisms involving endothelial cells, myeloid populations, cytokines, and chemokines.
  • Analysis of the interplay between the tumor microenvironment (TME), immunosuppression, and angiogenesis.

Main Results:

  • Compensatory adaptation to VEGF blockade involves activation of intrinsic or acquired angiogenic pathways, not gene mutations.
  • Hypoxia-regulated and immune-mediated mechanisms, including myeloid cell mobilization and cytokine circuits, preserve angiogenesis.
  • Galectins and glycosylated ligands play a significant role in promoting resistance to anti-VEGF therapies.

Conclusions:

  • Understanding compensatory angiogenic pathways is crucial for overcoming resistance to anti-angiogenic cancer treatments.
  • Targeting galectins and glycosylated ligands may offer strategies to attenuate resistance.
  • Combinatorial approaches simultaneously enhancing antitumor immunity and counteracting angiogenesis show promise.
Keywords:
AngiogenesisAnti-angiogenic therapyGalectinsHypoxiaImmunotherapyResistance

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