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A Low Dose, Multi-drug Cocktail for the Treatment of Metastatic and Resistant Breast Cancers

Published:
Lead Inventor: Marsha Rosner
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SUMMARY

  • An estimated 20-30% of breast cancer patients suffer from metastatic recurrence, which can be perpetuated by an overreliance on high doses of a single drug during initial treatment. In addition to promoting recurrence, ths treatment approach can also reduce drug sensitivity during relapse.
  • The Raf kinase inhibitor protein, RKIP, has previously been shown to block metastasis, but its in vivo kinase targets were unknown. The investigators used a combined mass spectroscopy and genomic approach to identify a RKIP-regulated network of target kinases involved in a metastatic signaling cascade. They then showed that the simultaneous inhibition of 4 kinases from the network mimicked the anti-metastatic effects of RKIP.
  • The invention is a method of treating metastatic cancer, using 4 different kinase inhibitors in the RKIP-network that target MEK1/2, p38 MAPK, JNK, and MLK 1/2/3/DLK. The invention drug cocktail can prevent metastasis, increase sensitivity in drug-resistant cancers, and offers a reduced risk of resistance over traditional monotherapy.
  • The investigators showed that the invention 4-drug cocktail stopped orthotopic and metastatic growth of triple negative breast cancer xenograft and syngeneic mouse models.

 

FIGURE

BoM1 C57/BL6 xenograft mice were treated for 4 weeks with either the full dose or half does of the 4-drug kinase inhibitor cocktail. Tumor growth is inhibited in mice treated with the invention 4 drug kinase inhibitor cocktail.

 

 

ADVANTAGES

ADVANTAGES

  • Can be used to treat triple negative breast cancer
  • Lower risk of drug resistant relapse than in treatment with monotherapies
  • Uses subtherapeutic dose of inhibitors

 

APPLICATIONS

  • Oncology combination therapy

 

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