Related Experiment Video

Updated: Feb 8, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

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Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies

Sabrina Rizzolio1,2, Gabriella Cagnoni1,2, Chiara Battistini1,2

  • 1Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.

The Journal of Clinical Investigation
|June 29, 2018
PubMed

Insights

Targeting cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Targeting oncogenes is a key cancer therapy strategy.
  • Acquired resistance to these therapies is a major clinical challenge.

Purpose of the Study:

  • To investigate the role of neuropilin-1 (NRP1) in acquired resistance to oncogene-targeted therapies.
  • To identify mechanisms by which NRP1 mediates resistance.
  • To explore therapeutic strategies combining oncogene inhibitors with NRP1 targeting.

Main Methods:

  • Treatment of melanoma, breast, stomach, and lung cancer cells with specific inhibitors (BRAF, HER2, MET).
  • Analysis of neuropilin-1 (NRP1) expression levels.
  • Investigation of downstream signaling pathways, including JNK, EGFR, and IGF1R.
  • Evaluation of combination therapies involving NRP1-interfering molecules.

Main Results:

  • Therapy with BRAF, HER2, or MET inhibitors led to increased NRP1 expression in cancer cells.
  • NRP1 upregulation was essential for acquired resistance to these targeted therapies.
  • NRP1 activated a JNK-dependent pathway, upregulating EGFR or IGF1R to sustain cell growth.
  • Combination therapy with NRP1 inhibitors improved drug efficacy and overcame resistance in preclinical models.

Conclusions:

  • Neuropilin-1 (NRP1) plays a critical role in mediating acquired resistance to oncogene-targeted therapies.
  • Targeting NRP1-dependent tyrosine kinase upregulation offers a promising strategy to enhance cancer treatment efficacy and prevent resistance.
  • Combination therapies involving NRP1 interference warrant further clinical investigation.
Keywords:
Breast cancerMelanomaOncologyProtein kinasesTherapeutics

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