O6-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer?

•MGMT promoter methylation predicts response to treatment with alkylating agents in patients with glioblastoma multiforme and possibly in small cell lung cancer and pulmonary neuroendocrine tumours.•In small cell lung cancer and large cell neuroendocrine carcinoma there's a high unmet need for new treatment options to improve the prognosis. Repurposing of drugs is an acceptable and innovative strategy in the advancement of treatment.•Temozolomide can be considered a 'personalized' treatment in lung cancer if the predictive role of MGMT is further confirmed.

This manuscript addresses the role of O6-methylguanine-DNA methyltransferase (MGMT) as a biomarker in the oncogenesis of cancer and the opportunity of turning this gene into a drugable target in neuroendocrine tumours of the lung. Studies in brain tumours conclude that MGMT promoter methylation is considered a strong predictive factor for a favourable outcome for treatment with temozolomide, e.g. alkylating agent. We conducted a systematic review of MGMT in non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC) and other pulmonary neuroendocrine tumours (NETs) to evaluate whether MGMT is a prognostic and/or predictive factor to select patients with lung cancer who can benefit from treatment with temozolomide. In NSCLC MGMT promoter methylation is not a prognostic and predictive factor, hence temozolomide has no place. In SCLC and NET patients with a MGMT promoter methylation benefit of temozolomide has to be confirmed.Temozolomide can be considered a 'personalized' treatment if the predictive role of MGMT is further confirmed.