We also show that SHP2, and PI3K/AKT, key downstream signaling components of multiple receptor tyrosine kinases (RTKs), regulate the phosphorylation of RNA pol II CTD via activation of CDK7, suggesting that targeting CDK7 may provide an elegant mechanism by which to block reactivation of multiple kinase pathways in breast cancer resistant to HER2-targeted therapies. The gene discussed is PIK3CA; the disease is breast carcinoma.