Combination of EGFR/HER2 Tyrosine Kinase Inhibition by BIBW 2992 and BIBW 2669 with Irradiation in FaDu Human Squamous Cell Carcinoma

Abstract

BIBW 2669 and BIBW 2992 showed a clear antiproliferative effect in vitro, whereas radiosensitization was only marginal. The present data are the first to show an effect of combined irradiation and dual EGFR/ErbB2 inhibition on tumor growth delay in vivo. Further preclinical investigations using fractionated irradiation schedules and local tumor control as experimental endpoint are needed to evaluate a possible curative potential for the combination treatment.

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

“…Afatinib has previously been shown to be effective in inhibiting the growth in vitro and in vivo of EGFR and HER-2 expressing tumours (23,46). In this study, afatinib inhibited the proliferation of all human colorectal tumour cell lines and the IC 50 values for afatinib were found to be up to 50 times lower compared to gefitinib (20) (data not shown).…”

“…4). Afatinib has previously been shown to cause cell cycle arrest in G0/G1 in other tumour cell lines (46). Treatment of the same cells with the cytotoxic drugs caused a blockade in the S and G2/M phase of the cell cycle (Fig.…”

Effects of Lovastatin Alone or Combined with Irradiation on Tumor Cells in Vitro and in Vivo

“…Cell Lines, Drug and Cytotoxicity Assays U87MG, an established human malignant glioma cell line, and FaDu, an established human hypopharyngeal squamous cell carcinoma line, are widely used for radiobiological research [4,23,28,29]. FaDu was cultured in supplemented DMEM and U87MG in MEM-EARLE medium.…”

Radiotherapy and inhibition of the EGF family as treatment strategies for prostate cancer: combining theragnostics with theragates

“…One of these inhibitors, BIBW2992 (afatinib), is a new irreversible dual specificity EGFR and HER2 inhibitor designed to covalently bind to Cys 773 of EGFR and Cys 805 of HER2 [46]. This inhibitor has demonstrated improvements over first-generation EGFR inhibitors in lung cancer and squamous cell carcinoma models [47][48][49]. Tolerability and pharmacokinetics of the inhibitor in patients have recently been investigated in a phase I study by Eskens et al [50], and phase II results reporting clinical activity of the compound have been described [51][52][53].…”