Search

A limited number of somatic mutations are known to trigger malignancy via chronic activation of cellular signaling pathways. High-throughput analysis of gene expression in cancer cells has revealed a plethora of deregulated genes by far exceeding the number of known genetic alterations. Targeted tumor therapy takes advantage of deregulated signaling in cancer. However, cancer cells may evade successful therapy, e.g., targeting oncogenic kinases, due to mutation of the target protein or to resistance mechanisms acting downstream of or parallel to the therapeutic block. To improve therapy and molecular diagnostics, we need detailed information on the wiring of pathway components and targets that ultimately execute the malignant properties of advanced tumors. Here we review work on Ras-mediated signal transduction and Ras pathway- responsive targets. We introduce the concept of signal-regulated transcriptional modules comprising groups of target genes responding to individual branches of the pathway network. Furthermore, we discuss functional approaches based on RNA interference for elucidating critical nodes in oncogenic signaling and the targets essential for malignancy. [ABSTRACT FROM AUTHOR]

While target genes deregulated by oncogenic Ras signaling were identified in a low-throughput manner in the past, recent expression profiling technologies have permitted transcriptome-wide screening approaches. The number of known deregulated genes has increased substantially, as has the proportion of candidate genes involved in various aspects of Ras-induced transformation. This chapter summarizes the results of gene expression profiling studies based on microarrays and advanced cDNA subtraction procedures [ABSTRACT FROM AUTHOR]