W941, a new PI3K inhibitor, exhibits preferable anti-proliferative activities against nonsmall cell lung cancer with autophagy inhibitors

SummaryThe PI3K pathway is aberrantly activated in many cancers and plays a critical role in tumour cell proliferation and survival, making it a rational therapeutic target. In the present study, the effects and the underlying mechanism of a new PI3K inhibitor, W941, were investigated in non-small-cell lung cancer (NSCLC). The results of this study showed that W941 inhibited the growth of A549 and Hcc827 cells with IC50 values of 0.12 and 0.23  μM, respectively, and that W941 markedly inhibited the growth of A549 xenograft tumours in a nude mouse model without decreasing body weight. Western blotting assays showed that W941 inhibited the phosphorylation of downstream proteins in the PI3K pathway (AKT, mTOR, p70S6K and 4EBP1) in both A54 9 and Hcc827 cells. In addition, after W941 treatment, a dose-dependent increase in the ratio of the LC3-II/I ratio was observed. When cells were pre-treated with chloroquine or bafilomycin A1, W941 increased the LC3-II/I ratio, suggesting that W941 acted as an autophagy inducer. Moreover, autophagy blockers enhanced apoptosis after W941 treatment, indicating that W941-induced autophagy actually protected the cells against its cytotoxicity. Our findings suggest that the combination of a PI3K inhibitor with an autophagy inhibitor might be a novel option for NSCLC treatment.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

Related Links:

Eur Rev Med Pharmacol Sci. 2021 Jul;25(14):4648. doi: 10.26355/eurrev_202107_26371.ABSTRACTThe article "MiR-1269a acts as an onco-miRNA in non-small cell lung cancer via down-regulating SOX6, by R.-H. Jin, D.-J. Yu, M. Zhong, published in Eur Rev Med Pharmacol Sci 2018; 22 (15): 4888-4897- DOI: 10.26355/eurrev_201808_15625-PMID: 30070324" has been withdrawn from the authors to some technical reasons (there are some errors and incorrect data). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15625.PMID:34337710 | DOI:10.26355/eurrev_202107_26371
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Source Type: research
Clin Lung Cancer. 2021 Jul 7:S1525-7304(21)00181-9. doi: 10.1016/j.cllc.2021.06.014. Online ahead of print.NO ABSTRACTPMID:34334297 | DOI:10.1016/j.cllc.2021.06.014
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Clin Lung Cancer. 2021 Jul 5:S1525-7304(21)00180-7. doi: 10.1016/j.cllc.2021.06.013. Online ahead of print.ABSTRACTBACKGROUND: Immune-checkpoint inhibitors (ICIs) have significantly improved outcome of advanced non-small cell lung cancer (aNSCLC) patients. However, their efficacy remains uncertain in uncommon histologies (UH).MATERIALS AND METHODS: Data from ICI treated aNSCLC patients (April,2013-January,2021) in one Institution were retrospectively collected. Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox proportional hazards regression model, respectively. Objective response rate (O...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
This study aims to seek ACT candidates for stage IB NSCLC and establish a nomogram to predict overall survival (OS) of specific patient for clinician's decision.METHOD: We performed a retrospective study on 16,765 patients (ACT group: n = 2,187; non-ACT group: n = 14,578) from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was assessed in two groups. We performed propensity-score matching for risk adjustment. The risk factors were identified and used to create nomogram. Concordance index (C-index), Hosmer-Lemeshow test, and calibration were applied to evaluate model performance. To furthe...
Source: Journal of Oncology - Category: Cancer & Oncology Authors: Source Type: research
Is the use of neoadjuvant immunotherapy combined with chemotherapy a safe and effective therapeutic option for patients with resectable non-small cell lung cancer?Translational Lung Cancer Research
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Hematology-Oncology Journal Article Source Type: news
ConclusionPopulation-based studies on routine data are possible using a distributed learning approach. This has the potential for decision support models for patients for whom supporting clinical trial evidence is not applicable.
Source: Journal of Medical Imaging and Radiation Oncology - Category: Radiology Authors: Tags: Radiation Oncology —Original Article Source Type: research
This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor.MethodsWe retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1  s [FEV1]  
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
The approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial.
Source: Clinical Oncology - Category: Radiology Authors: Tags: Original Article Source Type: research
This study aimed to investi gate the anti-cancer potential of PPAR-γ agonist Pioglitazone combined with COX-2 inhibitor Celelcoxib in NSCLC.Methods. Sixty adult Balb/C male mice were classified into sham control, disease control, and treatment groups. Mice were treated with Nicotine-derived nitrosamine ketone (NNK) (10  mg/kg), pioglitazone (10&20  mg/kg) and celecoxib (25&50  mg/kg). Weekly body weight, food intake, mean survival time&% increased life span were determined. Tumor weight and histopathological analysis were performed at the end of the study.Results. The significant tumor redu...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
More News: Cancer | Cancer & Oncology | Drugs & Pharmacology | Investigational New Drugs | Lung Cancer | Non-Small Cell Lung Cancer | Study