Current Cancer Drug Targets - Volume 8, Issue 6, 2008

Many of the currently available anti-cancer therapeutics are based on the concept of targeting tumor cells. However, the tumor stroma has also become a major focus of attention as a therapeutic target. An early attempt to target stromal components, in the 1990s, involved the matrix metalloproteinases (MMPs), that can be expressed by various cell types in the tumor stroma. MMPs were targeted in human cancer with Read More

Solid tumors are composed of the malignant cell itself (most commonly a carcinoma) and supporting cells that comprise the stroma. Significant stromal components include the extracellular matrix, supporting fibroblasts, vessels comprised of endothelium, pericytes and in some cases vascular smooth muscle, lymphatics and usually a major leukocyte infiltration. Indeed, macrophages may constitute up to 50% of the vi Read More

Wnt signaling plays an important role in cancer. Signaling is initiated by binding of Wnt ligands to Frizzled cell surface receptors and results in signaling via one of three pathways, the canonical Wnt pathway, which is the best characterized in both normal tissues and in cancer, and two non-canonical Wnt pathways, the Ca2+-dependent and the PCP pathways. Canonical Wnt signaling results in β-catenin accumulation in the c Read More

Recent findings have demonstrated that the tumor stroma actively contributes to tumorigenesis. The communication of malignant cells and tumor stromal components is orchestrated in part by a network of growth factors. One of these growth factors is transforming growth factor-β (TGF-β), a secreted multifunctional protein that acts in a highly cellular contextual manner. TGF-β can either stimulate or inhibit the tumor-promoti Read More

Eph receptors and their membrane-bound ephrin ligands are developmental cell guidance cues that direct cell migration and orchestrate patterning processes by modulating adhesive or repulsive cell properties. During the past two decades, an exponentially growing interest in their function has resulted in a considerably advanced understanding of the cellular and molecular principles of Eph function in normal and o Read More

Although it is evident that prostatic epithelial stem cells are responsible for maintaining normal and malignant tissues, it is well recognized that epithelial cells do not exist independently, but act in concert with the stromal microenvironment. Prostatic stroma is pivotal for normal development and homeostasis. The genetic and morphological changes that occur in prostatic epithelial cells, as they progress from a normal to mali Read More

Many recent advances in cancer therapy have been based on an understanding of the basic biology of the cancer cell itself, particularly with respect to abnormalities in various signalling pathways. It has become increasingly apparent that malignant cells exist in a complex cellular and extracellular microenvironment, which can play key roles in the initiation and maintenance of the malignant phenotype. These interactio Read More

Squamous cell carcinoma of the esophagus is one of the ten most frequent malignancies worldwide, characterized by a striking geographic variation in incidence. In North America and Europe, there has recently been a marked change in the epidemiology of this disease, where incidence rates for primary esophageal adenocarcinoma have increased in excess of any other human solid tumor. Although the reasons for this a Read More

Hsp90 (heat shock protein 90) is a molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory, metabolism, organization, and signaling proteins. Binding to Hsp90 is required for normal function of many proteins. In addition, Hsp90 has an extra-cellular function. It is found in two isotypes: α which is inducible and β which is constitutive. Tumor cells frequently over express Hs Read More

Resistance of human cancers to current treatment approaches remains a challenge in oncology. Therefore, there has been much interest in identifying molecular pathways that are responsible for primary or acquired resistance of cancers. Since most anticancer therapies, i.e. chemotherapy or radiotherapy, primarily act by triggering programmed cell death (apoptosis) in cancer cells, defects in apoptosis progr Read More