[PDF][PDF] Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2–dependent and other solid tumors
L Gandhi, R Bahleda, SM Tolaney… - Journal of Clinical …, 2014 - researchgate.net
Journal of Clinical Oncology, 2014•researchgate.net
Purpose Human epidermal growth factor (HER)–mediated signaling is critical in many
cancers, including subsets of breast and lung cancer. HER family members signal via the
phosphatidylinositide 3-kinase (PI3K)–AKT/protein kinase B–mammalian target of
rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple
contributors to tumor growth and invasion. On the basis of preclinical data suggesting
synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we …
cancers, including subsets of breast and lung cancer. HER family members signal via the
phosphatidylinositide 3-kinase (PI3K)–AKT/protein kinase B–mammalian target of
rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple
contributors to tumor growth and invasion. On the basis of preclinical data suggesting
synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we …
Purpose
Human epidermal growth factor (HER)–mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K)–AKT/protein kinase B–mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors.
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