Novel combinations based on epidermal growth factor receptor inhibition

In spite of recent advances in molecular biology leading to the introduction of clinically active novel agents, such as imatinib, erlotinib, and bevacizumab, therapy of the most common epithelial tumors, such as lung cancer, remains unsuccessful. The diversity of molecular abnormalities in these tumors-is felt to partly contribute to their resistance to therapy. It is, therefore, widely accepted-that one approach to improving the efficacy of cancer therapy is the development of rational, hypothesis-based - combinations of anticancer agents that may exhibit synergistic cytotoxic interactions. A number of empirical combination studies with, the epidermal growth factor receptor, and classic agents, undertaken in clinical trials, with disappointing results. It is, therefore, felt that preclinical combinations of epidermal growth factor receptor inhibitors and other novel agents, based on,sound knowledge of complementary signaling pathways whose concerted inhibition would-be hypothesized to inhibit growth, is the reasonable approach, in the future. A brief overview. of some of these pathways (mammalian target of rapamycin, vascular endothelial growth factor receptor, and ras/mitogen-activated protein kinase signaling) is provided in this review.