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Treatment of solid tumors using a combination of inhibitors

Breast cancerfibroblastImmuno-stimulatorsProstate cancerTLR-3 agonists

Introduction

Combination of an HIF-1 inhibitor and a TLR-3 agonist, to be used as an antitumor agent of a solid tumor, preferably for treating prostate cancer.

Technical features

The TLR-3 poly (I: C) agonist increases a specific HIF-1alpha isoform I.3 that induces VEGF expression and secretion and resistance to apoptosis in PC3 cell cultures, but not in the less aggressive LNCaP. Only by inducing the overexpression of HIF isoform I.3 did we induce the same pro-tumor responses to poly (I: C) also in LNCaP cells, demonstrating that the increase in HIF-1 is responsible for insensitivity to poly (I: C) treatment. (I: C) of the PC3. Consequently, a combined treatment of HIF inhibitors and TLR3 agonists could induce sensitization of very aggressive tumor cells. Despite promising in vitro, animal, and clinical trials data, there are to date no anti-cancer therapies based on either HIF-1 inhibitors or TLR-3 inducers. The data demonstrate that differences in baseline HIF-1a levels in different PCa cell histotypes underlie their heterogeneous response to TLR-3 activation-induced apoptosis, suggesting a strong correlation between different degrees of malignancy. expression of HIF and an effective response to TLR-3 agonists.

Possible Applications

  • Cancer treatment;
  • Possible induction of tumors in remission unlike patients treated in monotherapy (HIF-1 inhibitor or TLR-3 agonists);
  • Prognostic outcome;
  • Design of therapeutic goals for the most advanced stages of tumor progression.

Advantages

  • Overcoming tumor cell heterogeneities in vivo;
  • Therapeutic efficacy optimization;
  • Decrease toxicity.