“Scientists at the Department of Haematology and Oncology at the Nagoya Daini Red Cross Hospital in Japan have concluded that a drug called Zolinza (vorinostat) may improve outcomes for patients fighting indolent B-cell lymphomas like follicular lymphoma and mantle cell lymphoma.”
Tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa) are effective treatments for many patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, patients who also have a certain version of the BIM gene are resistant to TKIs. Vorinostat (Zolinza), a member of a family of drugs called histone deacetylase (HDAC) inhibitors, restored the antitumor activity of Iressa in EGFR-mutant NSCLC cells and in animal models of EGFR-mutant NSCLC that carried the resistant BIM version. Combining Zolinza with TKIs may therefore help circumvent TKI resistance in patients who have the resistant form of BIM.
Burns TF, Dobromilskaya I ... Tran PT, Rudin CM, Mol Cancer Res, Jan 30, 2013
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.
Ying J, Rahbar MH ... Forman MR, Gorlova OY, PLoS One, Feb 1, 2013
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.
Yu F, Lv M ... Yuan X, Lv Z, Int J Clin Exp Pathol, 2013
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.
Ragusa M, Vannucci J ... Crinò L, Puma F, Am J Clin Oncol, Jan 24, 2013
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.
Pillai R, Brodie SA ... Khuri FR, Brandes JC, Clin Cancer Res, Feb 5, 2013
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.
Nakagawa T, Takeuchi S... Sekido Y, Yano S, Cancer Res, Feb 4, 2013
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.