Non-small-cell lung cancer

Over the past decade, a multitude of targeted agents have been explored in the treatment of advanced non-small cell lung cancer (NSCLC). Thus far, two broad classes of agents have been implemented in clinical practice: (a) vascular endothelial growth factor (VEGF)-directed therapies and (b) antagonists of the epidermal growth factor receptor (EGFR). In the former category, the agent bevacizumab (a monoclonal antibody) has shown landmark improvements in survival when added to cytotoxic therapy. Small molecule tyrosine kinase inhibitors (TKI) targeting the VEGF receptor (i.e., sunitinib, sorafenib, and vandetanib) show activity in phase II clinical studies. With respect to EGFR-directed therapies, the TKIs gefitinib and erlotinib have shown significant benefit, and have uncovered valuable information about the biology of lung cancer. Outside of therapies directed specifically at VEGF- and EGFR-mediated signaling, trials evaluating insulin-like growth factor-1 receptor (IGF-IR)-targeting agents, cyclooxygenase-2 (COX-2) inhibitors, c-met inhibitors, irreversible pan-HER inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors are ongoing. Inhibitors of ALK show great promise in patients with the relevant gene translocation. Herein, the clinical development of novel therapies for NSCLC is described, including some discussion of relevant biomarkers and determination of synergy with both cytotoxic therapy and other targeted agents.

https://mct.aacrjournals.org/content/molcanther/9/7/1931.full.pdf

Targeted Therapies for Non–Small Cell Lung Cancer: An Evolving Landscape

https://doc.rero.ch/record/299904/files/mdp357.pdf

Insulin-like growth factor receptor 1 (IGF1R) expression and survival in surgically resected non-small-cell lung cancer (NSCLC) patients

The identification of certain molecular mechanisms underlying lung carcinogenesis and progression has led to the development of targeted agents against different families of growth factors and receptors. The epidermal growth factor receptor (EGFR) is one such target for therapeutic exploitation. Inhibition of EGFR downstream signaling can be accomplished through two primary mechanisms: (a) the direct blocking of intracellular kinase activity with small-molecule tyrosine kinase inhibitors (TKIs) (e.g., gefitinib, erlotinib) and (b) the blocking of EGFR ligand binding using antibodies directed against the extracellular domain of the receptor (e.g., cetuximab). Resistance to available EGFR-targeted treatments has emerged as a substantial clinical issue in non-small cell lung cancer (NSCLC). Several novel agents with the potential to overcome such resistance are currently in clinical development, including irreversible EGFR TKIs, monoclonal antibodies, and TKIs directed against multiple signaling pathways. Here we discuss the clinical application of the currently available EGFR-targeted agents in NSCLC, the underlying mechanisms of resistance, and the novel agents in clinical development that may overcome resistance.

The role of EGFR inhibition in the treatment of non-small cell lung cancer.

8036 Background: Increased expression of IGFR-1 has been hypothesized to impart resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Our objective was to associate clin...

Insulin-like growth factor receptor 1 (IGFR-1) and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib

22080 Background: The epidermal growth factor receptor (EGFR) signaling pathway has become an important target in lung cancer with the success of EGFR tyrosine kinase inhibitors (TKI). The IGFR-1 s...

Frequency of insulin-like growth factor 1 (IGFR-1) expression and correlation with clinical and selected molecular parameters in advanced non-small cell lung cancer (NSCLC) patients (pts)

16058 Background: Ovarian serous carcinoma (OSC) is the most common ovarian cancer sub-type and fourth leading cause of cancer-related deaths for women in the US. Unfortunately, more than two-third...

Serum biomarker discovery for ovarian serous carcinoma using novel proteomic methods

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Insulin-like growth factor receptor 1 (IGFR-1) and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib

Frequency of insulin-like growth factor 1 (IGFR-1) expression and correlation with clinical and selected molecular parameters in advanced non-small cell lung cancer (NSCLC) patients (pts)

Serum biomarker discovery for ovarian serous carcinoma using novel proteomic methods