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

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

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

PUBLICATIONS

• Yesilkanel et al. Combination therapy targeting the core MAP kinase network mimics breast cancer metastasis suppressor. Cell. 2019; submitted.
• Genetic Engineering and Biotechnology News feature

July 23, 2019

Pre-clinical in vivo

Patent Pending

Licensing,Co-development

Marsha Rosner