Phase 1 study of romidepsin plus erlotinib in advanced non-small cell lung cancer.

Purpose: Preclinical studies demonstrated anti-tumor efficacy of the combination of the histone deacetylase (HDAC) inhibitor romidepsin plus erlotinib in non-small cell lung cancer (NSCLC) models that were insensitive to erlotinib monotherapy. We therefore studied this combination in a phase 1 clinical trial in previously treated advanced NSCLC.

Methods: Romidepsin (8 or 10mg/m(2)) was administered intravenously on days 1, 8, and 15 every 28 days in combination with erlotinib (150 mg orally daily), with romidepsin monotherapy lead-in during Cycle 1.

Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks.

Epidermal growth factor receptor (EGFR) overexpression plays an important oncogenic role in cancer. Regular EGFR protein levels are increased in cancer cells and the receptor then becomes constitutively active. However, downstream signals generated by constitutively activated EGFR are unknown.

Tumor-selective, futile redox cycle-induced bystander effects elicited by NQO1 bioactivatable radiosensitizing drugs in triple-negative breast cancers.

Aims: β-Lapachone (β-lap), a novel radiosensitizer with potent antitumor efficacy alone, selectively kills solid cancers that over-express

Nad(p)h: quinone oxidoreductase 1 (NQO1). Since breast or other solid cancers have heterogeneous NQO1 expression, therapies that reduce the resistance (e.g.