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Updated: Jun 23, 2025

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Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches

Caterina Mancarella1, Andrea Morrione2, Katia Scotlandi1

  • 1Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

International Journal of Molecular Sciences
|June 19, 2024
PubMed

Insights

Therapeutic strategies targeting the insulin-like growth factor (IGF) system in cancer show limited efficacy due to its molecular complexity. Novel approaches must consider both intracellular and extracellular factors for effective IGF pathway blockade.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • The insulin-like growth factor (IGF) system is implicated in various pathologies, notably cancer.
  • Current therapeutic strategies targeting the IGF system in cancer have yielded disappointing clinical outcomes.
  • This suggests an underestimation of the IGF axis's molecular complexity and its interactions.

Purpose of the Study:

  • To review novel extracellular mechanisms contributing to IGF system dysregulation in cancer.
  • To explore the implications of these mechanisms for cancer hallmarks and therapeutic responses.
  • To highlight the need for combinatorial strategies addressing the IGF axis complexity.

Main Methods:

  • Literature review focusing on molecular and cellular mechanisms.
  • Analysis of genetic, transcriptional, and post-transcriptional regulation of the IGF system.
  • Investigation of extracellular factors influencing IGF signaling in cancer.

Main Results:

  • The efficacy of anti-IGF therapies is hampered by the intricate molecular network of the IGF axis.
  • Genetic and functional interactors significantly modulate IGF pathway activity.
  • Extracellular factors play a critical role in IGF system dysregulation and cancer progression.

Conclusions:

  • A comprehensive understanding of both intracellular and extracellular environments is crucial for deciphering IGF axis complexity in cancer.
  • Novel therapeutic strategies should integrate combinatorial approaches targeting the multifaceted IGF system.
  • Further research into IGF system interactions may reveal new avenues for cancer treatment.
Keywords:
IGF systemPROTACsRAGEcancerextracellular signalsextracellular vesiclestarget therapytumor microenvironment

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