Year-end Sale % OFF 
Abstract
Lung cancer is the leading cause of cancer mortality in both genders, with non-small cell lung cancer (NSCLC) accounting for about 85% of all lung cancers. At the time of diagnosis, the tumour is usually locally advanced or metastatic, shaping a poor disease outcome. NSCLC includes adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Searching for novel therapeutic targets is mandated due to the modest effect of platinum-based therapy as well as the targeted therapies developed in the last decade. The latter is mainly due to the lack of mutation detection in around half of all NSCLC cases. New therapeutic modalities are also required to enhance the effect of immunotherapy in NSCLC. Identifying the molecular signature of NSCLC subtypes, including genetics and epigenetic variation, is crucial for selecting the appropriate therapy or combination of therapies. Epigenetic dysregulation has a key role in the tumourigenicity, tumour heterogeneity, and tumour resistance to conventional anti-cancer therapy. Epigenomic modulation is a potential therapeutic strategy in NSCLC that was suggested a long time ago and recently starting to attract further attention. Histone acetylation and deacetylation are the most frequently studied patterns of epigenetic modification. Several histone deacetylase (HDAC) inhibitors (HDIs), such as vorinostat and panobinostat, have shown promise in preclinical and clinical investigations on NSCLC. However, further research on HDIs in NSCLC is needed to assess their anti-tumour impact. Another modification, histone methylation, is one of the most well recognized patterns of histone modification. It can either promote or inhibit transcription at different gene loci, thus playing a rather complex role in lung cancer. Some histone methylation modifiers have demonstrated altered activities, suggesting their oncogenic or tumour-suppressive roles. In this review, patterns of histone modifications in NSCLC will be discussed, focusing on the molecular mechanisms of epigenetic modifications in tumour progression and metastasis, as well as in developing drug resistance. Then, we will explore the therapeutic targets emerging from studying the NSCLC epigenome, referring to the completed and ongoing clinical trials on those medications.
Highlights
Lung cancer is the most common malignancy worldwide, with the highest mortality among all cancers
histone deacetylase (HDAC) overexpression can result in tumour suppressor gene (TSG) silencing and abnormal transcription as a result of the modified expression and/or mutations of genes encoding histone acetyltransferase (HAT) or HDAC enzymes or their binding congeners, which are directly connected to carcinogenesis [20] (Figure 1)
H3K4me2 and H3K18ac cellular levels were relatively low, and the identified histone modification trends were independent predictors of prognosis in ADC [42]. These findings strongly suggest that reduced cellular levels of specific histone modifications are likely to predict a shorter survival time
Summary
Lung cancer is the most common malignancy worldwide, with the highest mortality among all cancers. Exposure to cigarette smoke can cause an inflammatory response in a smokers’ airways, releasing several inflammatory mediators and growth factors (e.g., transforming growth factor β (TGF-β), epidermal growth factor receptor (EGFR), interleukin-1 (IL-1), IL-8, and granulocyte colony stimulating factor (G-CSF)). Such inflammation can last for decades after the cessation of smoking, leading to pathological and neoplastic changes [12]. EGFR and HER2 mutations are increased in non-smokers Such an observation adds to the findings that lung cancer in smokers and non-smokers arises via distinct pathogenic pathways [10]. According to the International Agency for Research on Cancer (IARC), both outdoor and PM air pollutants are Group 1 carcinogens [13]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
