Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

Sean P. Kennedy, Jeremy Z. R. Han, Neil Portman, Max Nobis, Jordan F. Hastings, Kendelle J. Murphy, Sharissa L. Latham, Antonia L. Cadell, Dushan Miladinovic, Gabriella R. Marriott, Yolande E. I. O'Donnell, Robert F. Shearer (+9 others)
2019 Breast Cancer Research  
The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer patients for two decades. However, the lack of response and the rapid onset of relapse in many patients now question the assumption that the ERBB2/ERBB3 heterodimer is the sole relevant effector target of these therapies.
doi:10.1186/s13058-019-1127-y pmid:30898150 pmcid:PMC6429830 fatcat:7lmw3v5snna3lhutirthk5b7gq