scholarly journals In vitro and in vivo synergistic efficacy of ceritinib combined with programmed cell death ligand‐1 inhibitor in anaplastic lymphoma kinase‐rearranged non‐small‐cell lung cancer

2020 ◽  
Vol 111 (6) ◽  
pp. 1887-1898
Author(s):  
Ping Du ◽  
Ting Hu ◽  
Zhuoling An ◽  
Pengfei Li ◽  
Lihong Liu
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

scholarly journals The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592199296
Author(s):  
Jingjing Qu ◽  
Quanhui Mei ◽  
Li Liu ◽  
Tianli Cheng ◽  
Peng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Challenges

The use of programmed cell-death protein 1 (PD-1)/programmed cell-death ligand 1 (PD-L1) inhibitors is the standard therapy for the first-line or second-line treatment of patients with non-small-cell lung cancer (NSCLC). In contrast to current traditional treatments such as chemotherapy or radiotherapy, anti-PD-1 and anti-PD-L1 treatments can directly attenuate tumour-mediated exhaustion and effectively modulate the host anti-tumour immune response in vivo. In addition, compared with traditional therapy, PD-1/PD-L1 inhibitor monotherapy can significantly prolong survival without obvious side effects in the treatment of advanced NSCLC. Ideally, several biomarkers could be used to monitor the safety and effectiveness of anti-PD-1 and anti-PD-L1 treatments; however, the current lack of optimal prognostic markers remains a widespread limitation and challenge for further clinical applications, as does the possibility of immune-related adverse events and drug resistance. In this review, we aimed to summarise the latest progress in anti-PD-1/anti-PD-L1 treatment of advanced NSCLC, worldwide, including in China. An exploration of underlying biomarker identification and future challenges will be discussed in this article to facilitate translational studies in cancer immunotherapy.

Rociletinib—An Investigational Therapy in Patients with Previously Treated EGFR Mutant-positive Non-small Cell Lung Cancer

2015 ◽  
Vol 11 (02) ◽  
pp. 122
Author(s):  
Giorgio Scagliotti ◽  
Silvia Novello ◽  
◽  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Anaplastic Lymphoma

Treatment for patients with non-small cell lung cancer (NSCLC) is being guided increasingly by driver mutations and, routinely, tumors from patients with adenocarcinoma are screened for mutations in the kinase domain of the epidermal growth factor receptor (EGFR) as well as for other genomic abnormalities (i.e. anaplastic lymphoma kinase [ALK] and ROS1 translocations). Effective, well-tolerated treatment options that specifically target theEGFRT790M mutation (the “gatekeeper” residue) in patients with NSCLC remains an unmet need. Rociletinib is an oral, irreversible, potent, covalent inhibitor of the activatingEGFRmutations (del19 and L858R) and the T790M resistance mutation; it also spares wild-type EGFR. TIGER-X is the first of the TIGER trial series, which is a clinical development program for rociletinib in patients with mutantEGFRNSCLC. This phase I–II study is evaluating rociletinib in patients who have progressed following their first and only EGFR-directed tyrosine kinase inhibitor (TKI) therapy who have developed the T790M mutation and in later-line T790M positive patients who have progressed on their second or later TKI therapy or subsequent chemotherapy. In the ongoing TIGER-X study, rociletinib has shown encouraging activity in patients withEGFRmutant-positive NSCLC and is well tolerated. Future aims of the ongoing TIGER programme include to investigate rociletinib treatment in other lines of therapy, determine whether rociletinib treatment can lead to an improvement in overall survival (OS) and to explore the potential benefits of combining rociletinib with other anti-cancer agents such as anti-programmed cell death protein and programmed cell death 1 ligand 1 monoclonal antibodies, mitogen-activated protein kinase enzyme inhibitors, vascular endothelial growth factor inhibitors, and c-Met inhibitors. Other aims include evaluating the outcome of progression-free survival associated with rociletinib treatment and determining the efficacy of rociletinib in patients with T790M negative status.

scholarly journals Clinically Relevant Chemotherapeutics Have the Ability to Induce Immunogenic Cell Death in Non-Small Cell Lung Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1474 ◽  
Author(s):  
Tal Flieswasser ◽  
Jinthe Van Loenhout ◽  
Laurie Freire Boullosa ◽  
Astrid Van den Eynde ◽  
Jorrit De Waele ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Immunogenic Cell Death ◽  
Small Cell Lung

The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and mafosfamide. The ICD hallmarks ATP, ecto-calreticulin, HMGB1, phagocytosis and maturation status of dendritic cells (DCs) were assessed in vitro. Furthermore, an in vivo vaccination assay on C57BL/6J mice was performed to validate our in vitro results. Docetaxel and the combination of docetaxel with carboplatin or cisplatin demonstrated the highest levels of ATP, ecto-calreticulin and HMGB1 in three out of four NSCLC cell lines. In addition, these regimens resulted in phagocytosis of treated NSCLC cells and maturation of DCs. Along similar lines, all mice vaccinated with NSCLC cells treated with docetaxel and cisplatin remained tumor-free after challenge. However, this was not the case for docetaxel, despite its induction of the ICD-related molecules in vitro, as it failed to reject tumor growth at the challenge site in 60% of the mice. Moreover, our in vitro and in vivo data show the inability of oxaliplatin to induce ICD in NSCLC cells. Overall with this study we demonstrate that clinically relevant chemotherapeutic regimens in NSCLC patients have the ability to induce ICD.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preparation And Evaluation
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