scholarly journals Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non–Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure

2018 ◽  
Vol 19 (6) ◽  
pp. e853-e859 ◽  
Author(s):  
David A. Barbie ◽  
Alexander Spira ◽  
Karen Kelly ◽  
Rita Humeniuk ◽  
Jun Kawashima ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Konstantinos Bromis ◽  
Kostakis Gkiatis ◽  
Irene Karanasiou ◽  
George Matsopoulos ◽  
Eustratios Karavasilis ◽  
...  

Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.


2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).


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