Pre‐clinical assessment of the impact of Erlotinib on adrenocortical cancer cells proliferation

Introduction: Adrenocortical carcinoma (ACC) has a poor prognosis and limited therapeutic options. The epidermal growth factor receptor (EGFR) expression was found to be a good discriminator between malignant and benign adrenal tumours, but was mutated only in 3–10% of ACC cases.

Aim: The aim of this study was to assess the effect of inhibition of EGFR with targeted therapies, i.e. Erlotinib (with and without EGF stimulation) on ACC cell proliferation in a pre-clinical setting.

Material and methods: Proliferation of ACC cells (H295R cell line and primary adrenocortical tumour culture) was assessed by Alamar blue assay after 24, 48, and 72 h of incubation with inhibitor at presence or absence of EGF. The expression and activation/inhibition of EGFR, and downstream signalling (Akt, Erk1/2, and mTORC1) was detected by western blot analysis.

Results: Despite the fact that the expression of EGFR was below the detection level using western blotting, activation of downstream signalling by EGF was shown by activation of Erk1/2 and Akt proteins. Erlotinib decreased cell proliferation rate after 24, 48, and 72 h of treatment, and the effect was enhanced in the presence of EGF. These effects were observed both in H295R cell line and in primary tumour culture.

Conclusions: Erlotinib alone inhibits cell proliferation and acts more potently if used jointly with EGF. We hypothesize that this effect may be associated with the change in cell metabolism caused by EGF. Therapy with anti-EGFR agents may be successful in ACC patients but requires further study.