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XL147 + trastuzumab
- Development stage
- Preclinical
- Lead developer
- Exelixis
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous
01
Overview
XL147 + trastuzumab is a **combination therapy** consisting of the small molecule pan-PI3K inhibitor XL147 and the monoclonal antibody trastuzumab (Herceptin), used experimentally to target HER2-positive breast cancer cells that are resistant to trastuzumab monotherapy. XL147 inhibits phosphatidylinositol 3-kinase (PI3K), counteracting PI3K pathway activation—which can confer trastuzumab resistance. Trastuzumab targets the extracellular domain of HER2 (ERBB2), inhibiting its signaling. In preclinical studies, the combination therapy **reduces proliferation, AKT activation, survivin and cancer stem cell fractions**, and triggers apoptosis in trastuzumab-resistant breast cancer models by modulating the HER2–PI3K–FoxO–survivin axis and downregulating pro-angiogenic factors including VEGF and IL-8[1][2].
- Brand names
- Herceptin
- Other names
- XL147 + Herceptin
02
Targets
PIK3CA (Phosphoinositide 3-kinase alpha)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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