title: O6-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer?
abstract: 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.
authors: Thoracic Oncology, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650, Edegem, Belgium. Electronic address: birgitta.hiddinga@uza.be.
authors: Birgitta I
authors: BI
authors: Hiddinga
authors: Molecular Pathology, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors: Patrick
authors: P
authors: Pauwels
authors: Thoracic Oncology, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors: Annelies
authors: A
authors: Janssens
authors: Thoracic Oncology, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors: Jan P
authors: JP
authors: van Meerbeeck
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D063646:Carcinogenesis / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Lung cancer; MGMT promoter methylation; Methylguanine-DNA methyltransferase; Neuroendocrine carcinoma; Neuroendocrine tumour; Non-small cell lung cancer; Small cell lung cancer; Temozolomide