Targeting Aberrant Signal Transduction Pathways in Lung Cancer

Abstract

Lung cancer is the deadliest form of cancer in the world and is most commonly associated with smoking. Current treatment strategies are largely ineffective due to advanced stage at diagnosis and the inherent therapeutic resistance of lung cancer cells. To improve patient outcomes, many studies have been designed to identify molecular alterations in lung cancer in order to develop new therapeutic strategies. Molecular alterations in lung cancer include genetic changes, epigenetic changes, and changes in the expression or activity of kinases that comprise signaling pathways within cells. Signaling pathways are attractive targets for lung cancer therapy because activation of signaling pathways contributes to tumor growth and therapeutic resistance, and constitutively active signaling commonly occurs in lung cancer. This review will discuss signaling pathways that are relevant to lung cancer. We will discuss specific signaling aberrations found in lung cancers, review the status of signaling inhibitors being developed for lung cancer, identify emerging targets, and provide recommendations for the development of agents designed to inhibit signal transduction.

L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

“…Securinine has previously been used in the clinic for the treatment of blood and nervous system diseases (32); therefore, the pharmacokinetic and pharmacodynamics properties of securinine are well understood. Identifying alterations in the signal transduction pathways that promote lung cancer, including epigenetic modifications, may reveal biomarkers that can be used for the diagnosis and treatment of lung cancer (33). The proteins encoded by the DKK genes represent the dickkopf family of proteins, which negatively regulate the Wnt signaling pathway (12).…”

Methods and biomarkers for the diagnosis and prognosis of cancer and other diseases: Towards personalized medicine

“…Currently, experimental drugs can be designed and targeted to different tissues in the body, or to specific types of cancer Gills et al, 2004;Hauff et al, 2005;Kreuter et al, 2004;Mendoza et al, 2005;Kleespies et al, 2006). Strategies under development will not only allow for selective identification of known malfunctioning signaling pathways (Adjei and Rowinsky, 2003;Hashemi et al, 2005), but also of entities that differ between normal and malignant phenotypes without necessarily knowing the molecular changes that are causing a malignancy (Maddika Mitrus et al, 2005;Robert et al, 2002).…”