FDG-PET Distinguishes Low- and High-Risk Lung Cancer Patients After Radiotherapy

Fluorodeoxyglucose-positron emission tomography (FDG-PET) scans may be able to detect early-stage non-small cell lung cancer (NSCLC) patients who are at high risk of treatment failure after stereotactic body radiation therapy (SBRT). A retrospective study examined patients with early-stage NSCLC who were ineligible for or refused surgery and were instead treated with SBRT. Patients with lower FDG-PET readings prior to SBRT treatment survived longer, and those whose FDG-PET readings changed more after SBRT were less likely to experience treatment failure. FDG-PET scans may therefore help identify which patients are at lower or higher risk of recurrence; high-risk patients may opt for additional treatment and/or more frequent surveillance after treatment. FDG-PET has shown similar predictive value in early-stage NSCLC treated with surgery.


FDG-PET Imaging May Help Predict Survival after Treatment of Advanced Lung Cancer

People with advanced non-small cell lung cancer (NSCLC) are usually treated with chemotherapy and radiotherapy. However, radiation interferes with the standard method of scanning for lung abnormalities, computed tomography (CT), making its measurements difficult to interpret. This creates the risk that leftover tumor fragments or new cancer spread may be overlooked. A different imaging methodology, fluorodeoxyglucose-positron emission tomography (FDG-PET), may be more accurate in such patients. FDG-PET measures sucrose uptake into cells. High uptake values indicate highly active cells, suggesting the presence of cancerous tissue. In a recent clinical trial, higher standardized uptake values (SUVs) in FDG-PET scans predicted lower survival in people with stage III NSCLC who had received chemotherapy and radiotherapy, suggesting that the method accurately detected cancerous tissue.


A Randomized Phase 2 Study of Paclitaxel and Carboplatin with or without Conatumumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer

This study evaluated the efficacy, safety, and pharmacokinetics of conatumumab combined with paclitaxel-carboplatin (PC) as first-line treatment for advanced non-small-cell lung cancer (NSCLC).

Although well tolerated, the addition of conatumumab to PC did not improve outcomes in unselected patients with previously untreated advanced NSCLC.


Inhibition of TWIST1 Leads to Activation of Oncogene-Induced Senescence in Oncogene Driven Non-Small Cell Lung Cancer

We recently demonstrated that the basic helix-loop-helix transcription factor Twist1 cooperates with mutant Kras to induce lung adenocarcinoma in transgenic mouse models and that inhibition of Twist1 in these models led to Kras-induced senescence. In the current study, we show that silencing of TWIST1 in KRAS mutant human NSCLC cell lines as well as in in EGFR mutation driven and c-Met amplified NSCLC cell lines resulted in dramatic growth inhibition and either activation of a latent oncogene-induced senescence program or in some cases, apoptosis.These findings suggest that silencing of TWIST1 in oncogene driver dependent NSCLC represents a novel and promising therapeutic strategy.


Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.


Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo an in vitro

This study shows that 188Re-MAG3-depreotide can inhibit the
proliferation and invasion of A549 cells and SPC-A1 cells. Treatment with 7.4MBq 188Re-MAG3-depreotide via tail vein can significantly
suppress the in vivo cancer growth and induce the apoptosis of cancer cells. These findings demonstrate that 188Re-MAG3-depreotide can
induce the apoptosis of NSCLC cells and directly kill the NSCLC cells, which provide evidence for the radiotherapy of NSCLC.


CHFR protein expression predicts outcomes to taxane-based first line therapy in metastatic NSCLC

Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non-small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival (OS) with taxane-based first-line chemotherapy in advanced stage NSCLC.

CHFR expression is a novel predictive marker of response and OS in NSCLC patients treated with taxane-containing chemotherapy.


Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcome in Resected Non-Small Cell Lung Cancer Patients

Surgery yields best results for non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC. Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC.

EGFR and KRAS mutations are frequent in adenocarcinomas and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.


EGFR-TKI resistance due to BIM polymorphism can be circumvented by in combination with HDAC inhibition

BIM (BCL2L11) is a BH3-only pro-apoptotic member of the Bcl-2 protein family. BIM upregulation is required for apoptosis induction by EGFR tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant forms of non-small cell lung cancer (NSCLC). Notably, a BIM deletion polymorphism occurs naturally in 12.9% of East Asian individuals, impairing the generation of the pro-apoptotic isoform required for the EGFR-TKIs gefitinib and erlotinib and therefore conferring an inherent drug resistant phenotype. We investigated whether the histone deacetylase (HDAC) inhibitor vorinostat could circumvent EGFR-TKI resistance in EGFR mutant NSCLC cell lines that also harbored the BIM polymorphism.

Our results show how HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI, in cases of EGFR mutant NSCLC where resistance to EGFR-TKI is associated with a common BIM polymorphism.