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Majority of cancer patients will die of metastases that develop from disseminated tumor cells (DTCs), months, years, or even decades after treatment. This pause in cancer progression suggests that, during these disease-free periods, DTCs may stop proliferating and survive in a dormant state. The mechanisms that determine whether tumor cells, after disseminating to target organs, will continue to proliferate,...
The search for effective cancer therapies is one of the foremost priorities of modern-day research. In recent times, enormous strides have been made in the understanding of the molecular events that underlie cancer progression and in the development of promising therapies against relevant molecular targets. The molecular signalling pathways that modulate tumourigenesis, especially those involved in...
Matrix metalloproteinases (MMPs) are a family of metalloendopeptidases that induce remodelling of extracellular matrix (ECM) and differentially cleave many soluble mediators that regulate cell physiology. Due to their matrix-degrading capabilities and elevated expression levels in both neoplastic and host cells in human cancer, MMPs have acquired considerable attention as targets for anti-cancer therapy...
The growth of brain tumors is dependent on the development of new vessels, a process called angiogenesis. In the clinic, neovascularization has been used as an independent prognostic marker, and is also a promising therapeutic target for treatments of patients with brain tumors. A large body of evidence demonstrates that brain tumor angiogenesis is an orchestrated process modulated by an array of...
As with most complex biological processes, angiogenesis requires the integration of a number of molecular signaling networks to coordinate multiple cues from both the extracellular tissue microenvironment as well as the cell’s interior. Thus an important area of angiogenesis investigation involves understanding the mechanisms that facilitate cooperation between multiple receptor–ligand signaling pathways...
The extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein (MAP) kinase module is a conserved signaling pathway that plays a major role in the control of cell proliferation, survival and differentiation. This pathway is typically turned on by engagement of growth factor receptors, which leads to the activation of the small GTPase Ras and to sequential phosphorylation and activation...
Platelet derived growth factor (PDGF) ligands and receptors are frequently overexpressed or exclusively expressed in many diverse tumors, compared with their non-malignant counterparts. This tumor specific expression often has diagnostic value and prognostic significance. There is now accumulating evidence that this PDGF expression is functionally relevant. It has been demonstrated that the constitutive...
The extracellular matrix protein fibronectin and its receptors (integrins α5β1, α4β1, α9β1, αvβ3, αvβ1, and αvβ6) play an active role in tumor growth and metastasis. Numerous tumors exhibit increased expression of fibronectin and its receptors, thereby promoting proliferation, survival, and motility of tumor cells as well as their subsequent metastasis. Additionally, fibronectin and integrins on endothelial...
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