Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways

This report uncovers that activation of Src lies downstream of multiple trastuzumab-resistance–driving pathways. The authors show that Src, a major mediator of PI3K and IGFR resistance pathways, also drives resistance caused by PTEN loss, revealing that Src is directly dephosphorylated by PTEN. Src inhibition can overcome de novo and acquired trastuzumab resistance, suggesting a potential therapeutic strategy broadly applicable in breast cancer.