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Conclusion Recent research has strengthened the basis for an intimate role of HER family kinases in a variety of cancers. In addition to propagating cytoplasmic signaling initiated by HER family receptor ligands, HER family members can also propagate signals initiated by multiple other signaling pathways and may serve as central nodes in conveying extracellular signals. Attenuation of HER family signaling...
Conclusions This review highlights the current knowledge of the alterations that occur in cancer and that involve integrins and integrin-activated pathways. Integrins are cell surface receptors for ECM proteins that mediate a variety of functions related to cell proliferation, differentiation, and survival. Although the specific functions of integrins and their ligands in cancer need to be further...
Conclusions The fact that VEGF is so precisely regulated is a testament to its central role in tumor angiogenesis, progression, and metastasis. The upstream pathways that regulate VEGF expression are valid targets for therapy as long as those pathways have some role in tumor growth. Although it is theoretically possible that argeting an upstream molecule could inhibit VEGF expression, the redundancies...
Conclusions The impressive amount of basic research data available on Pak1, the possibility that Pak1 is amplified or overexpressed in tumors and Pak1 ability to modulate motility and cell survival functions have generated considerable anticipation in the field of cancer research that strategies targeting Pak1 may lead to the design of target specific drugs. The identification of unique interacting...
Conclusion There are different options to inhibit Met activation and these are in part limited depending on the transforming phenotype. For example, inhibiting ligand/receptor interactions may be a useful approach when inhibiting a paracrine/autocrine mechanism but will show little effect on a gain-of-function mutation of Met. It still remains unknown as to how much Met inhibition is required to achieve...
Conclusions Overall these studies clearly demonstrate that NF-κB plays a critical role in tumorigenesis. Similarity, suppression of NF-κB has the ability to inhibit various steps in the tumorigenic process. Design of inhibitors that are pharmacologically safe will be critical for the treatment of cancer. Because of the multiple agents that activate NF-κB through diverse pathways, it is unlikely that...
Conclusions The Bcr-Abl oncoprotein affects and perturbs several signal transduction pathways within the leukemic cell. Based on mouse leukemia model studies, the Ras pathway is critically required for the onset of leukemia in these mice. The IL-3/GM-CSF- receptor pathways are also critically involved. Stimulation of secretion of these cytokines provide an autocrine growth mechanism. However in parallel,...
Conclusion The realisation that breast cancer growth is regulated by the hormone estrogen led to the development of tamoxifen as the first target-directed cancer drug. Clearly, there is considerable headway to be made in further elucidating estrogen receptor function, in particular in identifying the mechanisms underlying endocrine resistance. It is hoped that these studies will lead to the development...
Conclusions km23 is a novel motor receptor found to be linked to a TGFβ signaling pathway. Based upon our observations, we have constructed the following model (Fig. 3). Upon phosphorylation of km23 by TβRs, DIC is recruited to form a motor complex. This complex transports membrane vesicles containing TGFβ signaling components such as Smad2 along the microtubules to a new vesicular compartment. After...
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