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Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Background: Effective identification and development of new molecular methods for the diagnosis, treatment and prognosis of lung adenocarcinoma (LUAD) remains an urgent clinical need. DNA methylation patterns at cytosine bases in the genome are closely related to gene expression, and abnormal DNA methylation is frequently observed in various cancers. The ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) and promote locus-specific DNA methylation reversal. This study aimed to explore the role of the TET2 protein and its downstream effector, 5-hmC/5-mC DNA modification, in LUAD progression. Methods: The expression of TET2 was analysed by real-time PCR, Western blotting and immunohistochemistry. The 5-hmC DNA content was determined by a colorimetric kit. Activation of the cGAS-STING signalling pathway was evaluated by Western blotting. CCK-8, wound healing and Transwell assays were performed to evaluate the effect of TET2 on cell proliferation, migration and invasion abilities. A xenograft model was used to analyse the effect of TET2 on the tumorigenic ability of A549 cells. Results: TET2 overexpression decreased proliferation and metastasis of A549 and H1975 cells in vitro and in vivo. However, TET2 knockdown dramatically enhanced the proliferation, migration and invasion of A549 and H1975 cells. Mechanistically, activation of the cGAS-STING signalling pathway is critical for the TET2-mediated suppression of LUAD cell tumorigenesis and metastasis. Conclusion: In this study, we demonstrate a tumour suppressor role of TET2 in LUAD, providing new potential molecular therapeutic targets and clinical therapies for patients with non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Aim: Systemic inflammatory response is closely related to tumor progression. We retrospectively investigated relationships between systemic inflammatory scores, C‐reactive protein/albumin (CRP/Alb) ratio (CAR) and clinical characteristics in advanced non–small‐cell lung cancer (NSCLC) in 436 patients to find better clinical predictors of NSCLC prognosis. Methods: Blood specimens were collected 1 week before treatment to test for systemic inflammatory scores and albumin. Patients' overall survival (OS) was calculated via Kaplan–Meier method. Single‐factor log‐rank and multivariate Cox regression analyses and receiver operating characteristic curves were used to evaluate the prognostic significance of CAR and other systemic inflammatory indexes in predicting OS. Results: Kaplan–Meier method showed that Glasgow prognosis score (GPS), modified GPS (mGPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) were reliable prognostic factors for advanced NSCLC. CAR was positively correlated with GPS, mGPS, NLR, PLR and MLR in these patients. CAR was an independent risk factor for OS in advanced NSCLC, and was more closely associated with prognosis than were GPS, mGPS, NLR, PLR or MLR. Conclusion: In advanced NSCLC patients, CAR may be a better predictor of prognosis compared with other inflammatory markers. A prospective multicenter study is needed to verify these findings. [ABSTRACT FROM AUTHOR]

Mutations in the epidermal growth factor receptor (EGFR) have been found in more than 10% of non-small cell lung cancer (NSCLC) patients in North America. The vast majority of these differences are L858R point mutations in Exon 21. Currently, monoclonal antibodies directed against the extracellular domain of EGFR or small molecule/tyrosine kinase inhibitors (TKI) are the stalwarts of NSCLC therapy. Resistance, however, gradually develops because of the T790 mutation towards first and second generation TKIs. The third generation TKI AZD9291 (Osimertinib) has a high affinity for both activating and the acquired resistant mutation (T790 M) in EGFR, with a low affinity towards wild-type EGFR. Recent research, however, suggests that the EGFR (C797S) mutation in the tyrosine kinase domain is a likely cause of resistance to AZD9291. Another significant transformation mechanism associated with this resistance is erbB2 amplification. Our laboratory has developed a small kinase inhibitor, ER121 (MW: ∼500), that inhibits the erbB2/HER2 tyrosine kinases in addition to the EGFR C797S mutations. We have identified a TKI, ER121 targeting the mutant EGFR(T790 M). Using in vitro and in vivo models, examined the efficacy of ER121 on mutant EGFR cell lines. This has enabled us to establish that ER121 is well tolerated when administered orally and produces significant inhibitory activity against human cancers generated by mutant EGFR and amplified ErbB2. • ER121, a dual kinase inhibitor targets both mutant EGFR and activated erbB2. • ER121 inhibits EGFR mutants more effectively than AZD9291. • ER121 exhibits anti-tumor activity against Herceptin resistant breast tumors. [ABSTRACT FROM AUTHOR]

Background: Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, the MET exon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such as EGFR, KRAS, HER-2, BRAF, ALK and ROS1. The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence of MET exon 14 mutations with EGFR exon 20 insertion mutations has never been reported and the management of this subtype is not identified. Case presentation: A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive for MET exon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%), MET amplification (copy number 4.4), and EGFR exon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status. Conclusion: This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carrying MET alterations and EGFR exon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context. [ABSTRACT FROM AUTHOR]

Aim To assess the prognostic value of mediastinal lymph node metastases ( N2 disease), carcinoembryonic antigen ( CEA) levels and C-reactive protein ( CRP) in non-small cell lung cancer ( NSCLC), according to the 7th edition of the TNM classification. Methods Newly diagnosed stage III-IV NSCLC were enrolled, including 75 patients with malignant pleural effusion. The relationship between serum CRP levels and other relevant variables such as sex, Eastern Cooperative Oncology Group status, smoking status, initial staging, N2 disease, serum albumin, white blood cell count, platelet count, CEA, comorbidity and pathology were analyzed. Univariate and multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. Results Of the 127 patients enrolled, 55 (43%) had elevated CRP levels. There was a significant correlation between serum CRP level and platelet count ( P = 0.011). Median overall survival ( OS) in the normal CRP group was significantly longer than in the high CRP group (15.7 months vs 9.1 months, P = 0.013). Hypoalbuminemia ( P = 0.047), higher CEA ( P = 0.043) and N2 disease ( P = 0.040) were additional prognostic factors on univariate analysis. On multivariate analysis an elevated CRP serum level ( HR = 1.796; P = 0.005), higher CEA ( HR = 1.563; P = 0.031) and N2 disease ( HR = 1.723; P = 0.012) were independent prognostic factors for poor survival. Conclusion High levels of serum CRP and CEA, and N2 disease are independent prognostic indicators for the survival of patients with stage III- IV NSCLC. [ABSTRACT FROM AUTHOR]

Background: Unprecedented durable responses are identified in clinical studies to target the signaling of programmed cell death protein-1 (PD-1) as well as its ligand (PD-L1) in patients with squamous-cell non-small cell lung cancer (NSCLC). However, factors predicting the patient subtypes that are responsive to PD-1/PD-L1inhibitors have not been fully understood yet. Biomarkers, like PD-L1 expression, tumor mutational burden(TMB), DNA mismatch repair deficiency (dMMR), and tumor-infiltrating lymphocytes (TILs), have been utilized to select patients responsive to PD-1/PD-L1inhibitors in the clinic, but each of them has limited use. Lung adenocarcinoma patients with a mutation of TP53 or KRAS, particularly those with co-mutations of TP53 and KRAS, can benefit from anti–PD-1 treatment. Case presentation: In this study, the co-mutations of TP53 and KRAS in a 64-year-old non-smoking man with squamous-cell NSCLC patient was described using the next-generation sequencing (NGS) technology. The patient was treated with the pembrolizumab combined with gemcitabine as the salvage therapy, and a marked partial response could be attained, which had persisted for over 7 months. Conclusion: In addition to testing common driving genes, like EGFR, ALK, ROS1 and BRAF, both TP53, and KRAS should also be considered in advanced or metastatic squamous-cell NSCLC.TP53 and KRAS co-mutations in squamous-cell NSCLC can be a potential factor to assess possible response to PD-1 blockade immunotherapy, but further studies with more cases are needed to confirm the prediction power. [ABSTRACT FROM AUTHOR]