scholarly journals Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models

2015 ◽  
Vol 1 (2) ◽  
pp. 00028-2015 ◽  
Author(s):  
Roland Hubaux ◽  
Fabian Vandermeers ◽  
Jean-Philippe Cosse ◽  
Cecilia Crisanti ◽  
Veena Kapoor ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Mouse Models ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Line Therapy

With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC.The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development).We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models.Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies.

scholarly journals A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma

2021 ◽  
pp. LMT47
Author(s):  
Jerónimo Rafael Rodríguez-Cid ◽  
Sonia Carrasco-Cara Chards ◽  
Iván Romarico González-Espinoza ◽  
Vanessa García-Montes ◽  
Julio César Garibay-Díaz ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Objective Response ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
Total Study Population ◽  
Cell Lung Carcinoma

Background: Immunotherapy has demonstrated an improved overall survival (OS) and progression-free survival (PFS) as second-line treatment and subsequent lines compared with chemotherapy.  Materials and methods: This was a retrospective review among eight medical centers comprising 100 patients with a confirmed diagnosis of non-small-cell lung carcinoma, in their second-line treatment or beyond with immune checkpoints inhibitors treatment. The current study aimed to analyze effectiveness of immunotherapy in second-line treatment or further in the Mexican population, using PFS rate, OS rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. Results: In total, 100 patients met the criteria for enrollment in the current study. From the total study population, 49 patients (49.0%) were male and 51 (51.0%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the study. A total of 61 patients (61.0%) had partial response; 11 (11.0%) stable disease; 2 (2.0%), complete response, 4 (4.0%), progression; and 22 (22.0%) were nonevaluable. We found a median PFS of 4 months (95% CI: 3.2–4.7 months) and an OS of 9 months (95% CI: 7.2–10.7 months). Conclusion: The response to immunotherapy is similar, with an improvement in OS and PFS, independent of which drug is used. Patients using nivolumab had a better survival, although that was not statistically significant.

scholarly journals Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 430 ◽  
Author(s):  
Roberta Gualdani ◽  
Marie de Clippele ◽  
Ikram Ratbi ◽  
Philippe Gailly ◽  
Nicolas Tajeddine
Keyword(s):  
Cancer Progression ◽  
Lung Carcinoma ◽  
Transient Receptor Potential ◽  
Small Cell Lung Carcinoma ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Calcium Entry ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Store Operated Calcium Entry

Cisplatin (CDDP) is one of the principal chemotherapeutic agents used for the first-line treatment of many malignancies, including non-small cell lung carcinoma (NSCLC). Despite its use for over 40 years, its mechanism of action is not yet fully understood. Store-operated calcium entry (SOCE), the main pathway allowing Ca2+ entry in non-excitable cells, is involved in tumorogenesis, cancer progression and chemoresistance. It has become an attractive target in cancer treatment. In this study, we showed that siRNA-mediated depletion of stromal interaction molecule 1 (STIM1) and transient receptor potential channel 1 (TRPC1), two players of the store-operated calcium entry, dramatically reduced CDDP cytotoxicity in NSCLC cells. This was associated with an inhibition of the DNA damage response (DDR) triggered by CDDP. Moreover, STIM1 depletion also reduced CDDP-dependent oxidative stress. In parallel, SOCE activation induced Ca2+ entry into the mitochondria, a major source of reactive oxygen species (ROS) within the cell. This effect was highly decreased in STIM1-depleted cells. We then conclude that mitochondrial Ca2+ peak associated to the SOCE contributes to CDDP-induced ROS production, DDR and subsequent apoptosis. To the best of our knowledge, this is the first time that it is shown that Ca2+ signalling constitutes an initial step in CDDP-induced apoptosis.

scholarly journals Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Poulami Khan ◽  
Apoorva Bhattacharya ◽  
Debomita Sengupta ◽  
Shruti Banerjee ◽  
Arghya Adhikary ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rna Polymerase Ii ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Small Cell Lung ◽  
Incurable Cancer ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition

AbstractConventional chemotherapeutic regimens are unable to prevent metastasis of non-small cell lung carcinoma (NSCLC) thereby leaving cancer incurable. Cancer stem cells (CSCs) are considered to be the origin of this therapeutic limitation. In the present study we report that the migration potential of NSCLCs is linked to its CSC content. While cisplatin alone fails to inhibit the migration of CSC-enriched NSCLC spheroids, in a combination with non-steroidal anti inflammatory drug (NSAID) aspirin retards the same. A search for the underlying mechanism revealed that aspirin pre-treatment abrogates p300 binding both at TATA-box and initiator (INR) regions of mTOR promoter of CSCs, thereby impeding RNA polymerase II binding at those sites and repressing mTOR gene transcription. As a consequence of mTOR down-regulation, Akt is deactivated via dephosphorylation at Ser473 residue thereby activating Gsk3β that in turn causes destabilization of Snail and β-catenin, thus reverting epithelial to mesenchymal transition (EMT). However, alone aspirin fails to hinder migration since it does not inhibit the Integrin/Fak pathway, which is highly activated in NSCLC stem cells. On the other hand, in aspirin pre-treated CSCs, cisplatin stalls migration by hindering the integrin pathway. These results signify the efficacy of aspirin in sensitizing NSCLC stem cells towards the anti-migration effect of cisplatin. Cumulatively, our findings raise the possibility that aspirin might emerge as a promising drug in combinatorial therapy with the existing chemotherapeutic agents that fail to impede migration of NSCLC stem cells otherwise. This may consequently lead to the advancement of remedial outcome for the metastatic NSCLCs.

Sign in / Sign up

Export Citation Format

Share Document