Research conducted by an international team of scientists discovered a mechanism that leads to Herceptin resistance, representing a significant clinical obstacle to successfully treating HER2-positive breast cancer. They also identified a new approach to potentially overcome it.
The work is published online in Nature Communications.The researchers found increased signaling by IGF2/IRS1 (genes involved in regulating cell proliferation, growth, migration, differentiation and survival) in the HER2-positive breast cancer cells poorly responding to Herceptin. Further studies showed that disruption of a negative feedback loop formed by an important protein, FOXO3a, and several miRNAs that are controlled by FOXO3a causes abnormal activation of the IGF2/IRS1 signal, leading to Herceptin resistance.
"Resistance to Herceptin frequently occurs and currently represents a major clinical challenge for successful treatment of HER2-positive breast cancer,” notes explains Bolin Liu, MD, Professor of Genetics at LSU Health New Orleans’ School of Medicine and Stanley S. Scott Cancer Center. “Data presented in the study not only improve our understanding of the molecular mechanism through which IGF-1R signaling activation leads to Herceptin resistance, but also promote identification of precision therapies to reverse the resistance phenotype.”
