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.
Objectives/Hypothesis We studied the influence of the neutrophil‐to‐lymphocyte ratio (NLR) and anemia on the response to induction chemotherapy (IC) and survival outcomes in laryngeal cancer patients treated with a preservation protocol. Study Design Retrospective single‐center case series. Methods We analyzed patients with T3 laryngeal cancer treated with IC using a preservation protocol. The NLR and hemoglobin levels were assessed before treatment and after IC. The response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumours 1.1 and World Heath Organization standards. The oncological endpoints were overall survival (OS) and disease‐free survival (DFS). Results Sixty‐eight patients were analyzed. The median NLR and hemoglobin levels before and after IC were 2.76 and 14.5 g/dL, and 2.01 and 11.6 g/dL, respectively. The NLR and anemia before treatment were not correlated, and they were not associated with the response to chemotherapy. However, an NLR > 5 and anemia before treatment were both associated with shorter OS and DFS. Notably, they were the only factors found to be significantly associated with survival outcomes. Conclusions In laryngeal cancer, patients treated with a preservation protocol, a high NLR ratio, and anemia before IC were associated with shorter survival, independently of the response to chemotherapy. Level of Evidence 4 Laryngoscope, 130:E144–E150, 2020
Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells.Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated.Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival.Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.
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