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GDC-0941 + pemetrexed + cisplatin + bevacizumab

Development stage
Phase 1
Lead developer
Genentech
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

This is an **experimental combination therapy** consisting of the following agents: - **GDC-0941 (pictilisib)**: a small-molecule, orally bioavailable, ATP-competitive **pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor**, targeted against PI3K isoforms p110α and p110δ. It blocks PI3K pathway activation, thereby inhibiting downstream AKT signaling and tumor cell proliferation. - **Pemetrexed**: a **multitargeted antifolate** chemotherapy agent that inhibits several folate-dependent enzymes, notably thymidylate synthase, and is widely used to treat lung and other cancers. - **Cisplatin**: a **platinum-based chemotherapy drug** that induces DNA crosslinking, leading to apoptosis of rapidly dividing cells. - **Bevacizumab**: a **humanized monoclonal antibody against vascular endothelial growth factor A (VEGF-A)**, inhibiting tumor angiogenesis and thus tumor growth and metastatic spread. This combination is under investigation for advanced malignancies, especially solid tumors like non-small cell lung cancer, based on the synergistic effects of targeting angiogenesis (bevacizumab), DNA synthesis and repair inhibition (cisplatin, pemetrexed), and PI3K signaling (GDC-0941)[3][9][2].

Other names
pictilisib
02

Targets

DHFR (Dihydrofolate reductase)GART (GAR transformylase)TS (Thymidylate synthase)VEGFA (Vascular endothelial growth factor A)DNAPIK3CA (Phosphoinositide 3-kinase alpha)PIK3CD (Phosphatidylinositol 3-kinase delta)

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