Pathway of the Month
The mTOR Pathway in Lung Cancer and Implications for Therapy and Biomarker Analysis
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulatory protein in normal cell growth, survival, metabolism, development, and angiogenic pathways. Deregulation of these processes is a required hallmark of cancer, and dysregulation of mTOR signaling frequently occurs in a wide variety of malignancies, including lung cancer. Targeting of mTOR is thus an attractive strategy in the development of therapeutic agents against lung cancer. In this review, the mTOR-signaling pathway is described, highlighting opportunities for therapeutic intervention and biomarker analysis, and clinical trials in lung cancer including both non–small cell lung cancer and small cell lung cancer.The Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Lung Cancer: Still Following the Right TRAIL?
Tumor necrosis factor-related apoptosis-inducing ligand is a type II membrane-bound protein whose C-terminal extracellular domain shows clear homology to other tumor necrosis factor family members. It is constitutively expressed on macrophages, T cells, natural killer cells, and dendritic cells and selectively kills transformed cells leaving most of the normal cells alone. This selectivity has led to great interest in it use as a therapeutic agent for the treatment of malignancy. In this review, this critical pathway is described, highlighting its mechanistic manipulation for therapeutic benefit and the recent phase I and II trials in lung cancer that have been performed or are currently ongoing are also discussed.The CTC-Chip: An Exciting New Tool to Detect Circulating Tumor Cells in Lung Cancer Patients
Circulating tumor cells (CTCs) are rare cells that originate from a malignancy and circulate freely in the peripheral blood. The ability to capture and study CTCs is an emerging field with implications for early detection, diagnosis, determining prognosis and monitoring of cancer, as well as for understanding the fundamental biology of the process of metastasis. Here, we review the development and initial clinical studies with a novel microfluidic platform for isolating these cells, the CTC-chip, and discuss its potential uses in the study of lung cancer.The CXCR4/SDF-1 Chemokine Receptor Axis: A New Target Therapeutic for Non-small Cell Lung Cancer
Chemokines are proinflammatory chemoattractant cytokines that regulate cell trafficking and adhesion. The CXCR4 chemokine receptor and its ligand, stromal cell derived factor (SDF-1), constitute a chemokine/receptor axis that has attracted great interest because of an increasing understanding of its role in cancer, including lung cancer. The CXCR4/SDF-1 complex activates several pathways that mediate chemotaxis, migration and secretion of angiopoietic factors. Neutralization of SDF-1 by anti-SDF-1 or anti-CXCR4 monoclonal antibody in preclinical in vivo studies results in a significant decrease of non-small cell lung cancer metastases.Insulin-Like Growth Factor and Lung Cancer
Lung cancer is the leading cause of cancer-related death in the United States. Despite the availability of several cytotoxic and a few molecularly targeted agents, the outlook for patients with advanced non-small cell lung cancer continues to be dismal. Novel approaches are desperately needed. The insulin-like growth factor (IGF) pathway plays an important role in a number of human malignancies contributing to unregulated cell proliferation. The IGF pathway has several targets for therapeutic intervention.
