The dual role of DNA repair protein MGMT in cancer prevention and treatment

Bai, Peiying; Fan, Ting; Sun, Guizhi; Wang, Xin; Zhao, Lu; Zhong, Rugang

doi:10.1016/j.dnarep.2023.103449

Cited by 23 publications

(18 citation statements)

References 154 publications

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“…Detecting the hypermethylation of DAPK can have diagnostic and prognostic implications for HNSCC patients 44 . MGMT is a DNA repair enzyme that plays a critical role in removing alkyl adducts from the O‐6 position of guanine, which can be induced by DNA‐damaging agents, including chemotherapy 45 . Methylation of the promoter of the MGMT gene can be silenced, by reducing the repair capacity of the cell and potentially affecting the response treatments inducing DNA damage.…”

Section: Diagnosis In Personalized Medicinementioning

confidence: 99%

Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments

Jayawickrama,

Ranaweera,

Pradeep

et al. 2024

Cancer Reports

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BackgroundPrecision healthcare has entered a new era because of the developments in personalized medicine, especially in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC). This paper explores the dynamic landscape of personalized medicine as applied to HNSCC, encompassing both current developments and future prospects.Recent FindingsThe integration of personalized medicine strategies into HNSCC diagnosis is driven by the utilization of genetic data and biomarkers. Epigenetic biomarkers, which reflect modifications to DNA that can influence gene expression, have emerged as valuable indicators for early detection and risk assessment. Treatment approaches within the personalized medicine framework are equally promising. Immunotherapy, gene silencing, and editing techniques, including RNA interference and CRISPR/Cas9, offer innovative means to modulate gene expression and correct genetic aberrations driving HNSCC. The integration of stem cell research with personalized medicine presents opportunities for tailored regenerative approaches. The synergy between personalized medicine and technological advancements is exemplified by artificial intelligence (AI) and machine learning (ML) applications. These tools empower clinicians to analyze vast datasets, predict patient responses, and optimize treatment strategies with unprecedented accuracy.ConclusionThe developments and prospects of personalized medicine in HNSCC diagnosis and treatment offer a transformative approach to managing this complex malignancy. By harnessing genetic insights, biomarkers, immunotherapy, gene editing, stem cell therapies, and advanced technologies like AI and ML, personalized medicine holds the key to enhancing patient outcomes and ushering in a new era of precision oncology.

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Section: Diagnosis In Personalized Medicinementioning

confidence: 99%

Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments

Jayawickrama,

Ranaweera,

Pradeep

et al. 2024

Cancer Reports

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“…MGMT is a DNA repair enzyme that reverses alkylating agent‐induced DNA damage by transferring a methyl group from the guanine O6 site to its cysteine residue to repair damaged O6 methylguanine nucleotides 75,76 . MGMT plays an important protective role in normal cells and its overexpression is one of the major mechanisms leading to drug resistance in GCs 77 .…”

Section: Advances In Chemotherapy For Gliomamentioning

confidence: 99%

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

Liu,

Yang,

et al. 2024

CNS Neurosci Ther

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Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood–brain barrier and the occurrence of the drug‐resistant gene O6‐methylguanine‐DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

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“…One of the lesserknown targets of HR-E6 is the protein MGMT (O-6-Methylguanine-DNA Methyltransferase) (Figure 2). This protein is a methyltransferase that removes the alkyl group covalently bonded to DNA, thereby preventing mutations, aberrations, and breaks [148]. E6 degrades MGMT in an E6AP-dependent manner and, by doing this, disables another DNA repair pathway [149].…”

Section: Dna Damage Repairmentioning

confidence: 99%

Comparative Analysis of Alpha and Beta HPV E6 Oncoproteins: Insights into Functional Distinctions and Divergent Mechanisms of Pathogenesis

Skelin,

Tomaić

2023

Viruses

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Human papillomaviruses (HPVs) represent a diverse group of DNA viruses that infect epithelial cells of mucosal and cutaneous tissues, leading to a wide spectrum of clinical outcomes. Among various HPVs, alpha (α) and beta (β) types have garnered significant attention due to their associations with human health. α-HPVs are primarily linked to infections of the mucosa, with high-risk subtypes, such as HPV16 and HPV18, being the major etiological agents of cervical and oropharyngeal cancers. In contrast, β-HPVs are predominantly associated with cutaneous infections and are commonly found on healthy skin. However, certain β-types, notably HPV5 and HPV8, have been implicated in the development of non-melanoma skin cancers in immunocompromised individuals, highlighting their potential role in pathogenicity. In this review, we comprehensively analyze the similarities and differences between α- and β-HPV E6 oncoproteins, one of the major drivers of viral replication and cellular transformation, and how these impact viral fitness and the capacity to induce malignancy. In particular, we compare the mechanisms these oncoproteins use to modulate common cellular processes—apoptosis, DNA damage repair, cell differentiation, and the immune response—further shedding light on their shared and distinct features, which enable them to replicate at divergent locations of the human body and cause different types of cancer.

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The dual role of DNA repair protein MGMT in cancer prevention and treatment

Cited by 23 publications

References 154 publications

Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments

Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

Comparative Analysis of Alpha and Beta HPV E6 Oncoproteins: Insights into Functional Distinctions and Divergent Mechanisms of Pathogenesis

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