Current Drug Targets - Volume 11, Issue 9, 2010

Despite a recent decline in incidence, breast cancer remains as one of the most frequently diagnosed cancers and the second leading cause of cancer related deaths in American women [1]. There are a number of challenges that impact our ability to effectively treat this disease. First, breast cancer is a heterogeneous collection of diseases that demonstrate diverse histopathologies [2], genomic alterations [3], gene ex Read More

Rho GTPase signaling is altered in human breast tumors, and elevated expression and activation of Rho GTPases correlate with tumor progression, metastasis, and poor prognosis. Here we review the evidence that Rho signaling functions as a key regulator of cell cycle, mitosis, apoptosis, and invasion during breast cancer growth and progression and discuss whether these pleiotropic actions enhance or limit the targetability of Read More

As modulators of gene expression, microRNAs (miRNAs) are essential for normal development. Not surprisingly, aberrant expression of miRNAs is associated with many diseases, including cancer. Studies of various breast cancer subtypes have demonstrated that, like gene expression profiles and pathological differences, miRNA profiles can distinguish various tumor subtypes. Over the last few years, roles for miRNAs during m Read More

Aberrant activation of the Wnt/β-catenin signaling pathway is a hallmark of many tumors, including breast cancer. In the normal breast, tightly regulated expression of Wnt/β-catenin pathway components, including Wnts and the APC tumor suppressor, dictates its role in balancing stem cell self-renewal, maintenance and differentiation during embryonic and postnatal development. Therefore, not surprisingly, dysregulation o Read More

Transforming Growth Factor β (TGFβ) signaling influences most aspects of cellular function in addition to playing a major role in organ development, remodeling, and repair. Given the wide range of effects induced by TGFβ, it is not surprising that alterations in TGFβ signaling have been implicated in development and progression of many different cancer types. Within the context of breast cancer itself, TGFβ is known to have a dual Read More

The hedgehog signal transduction network is a critical regulator of metazoan development. Inappropriate activation of this network is implicated in several different cancers, including breast. Genetic evidence in mice as well as molecular biological studies in human cells clearly indicate that activated signaling can lead to mammary hyperplasia and, in some cases, tumor formation. However, the exact role(s) activated hedge Read More

For decades, it has been recognized that cancer cells display a unique metabolism; specifically, cancer cells have been shown to preferentially utilize glycolysis instead of mitochondrial respiration. This phenomenon is commonly known as the “Warburg effect” after Otto Warburg who first made this observation in 1927. The discovery of the Warburg effect has lead to new methods of detection and differentiation of cancero Read More

The insulin-like growth factors (IGFs) acting via the type I IGF receptor (IGF-1R) regulate cancer cell proliferation, survival, metabolism and metastasis. Drugs targeting the IGF-1R are being tested in human clinical trials for cancer therapy and it seems likely that this class of drugs could be approved soon. Recent data suggests that insulin receptor, which is closely related to IGF-1R, should also be targeted to maximally in Read More

Inflammation within the tumor microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. The cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) are critical mediators of the inflammatory response. Numerous studies have also linked these cytokines to breast cancer progression. As a result, the mechanisms b Read More

The hypothesis that tumors may originate from a rare population of cancer stem cells (CSCs) has gained tremendous popularity in recent years and is supported extensively by several pioneering works. Cancer therapies targeting CSCs have unlimited potential for relapse free survival of cancer patients. As a result, knowledge of biological pathways that govern CSCs is very important and this review is focused on the biology of C Read More

Macrophage Stimulating Protein (MSP) is the only known ligand for the receptor tyrosine kinase Ron. The MSP/Ron pathway is involved in several important biological processes, including macrophage activity, wound healing, and epithelial cell behavior. A role for MSP/Ron in breast cancer has recently been elucidated, wherein this pathway regulates tumor growth, angiogenesis, and metastasis. Here, we review the recent litera Read More

G protein-coupled receptors (GPCRs) comprise a large family of membrane receptors involved in signal transduction. These receptors are linked to a variety of physiological and biological processes such as regulation of neurotransmission, growth, cell differentiation and oncogenesis among others. Some of the effects of GPCRs are known to be mediated by the activation of MAPK pathways. Several GPCRs are also able to tra Read More

Malignant cell transformation is caused by mutations in distinct key regulatory genes involved in cell growth, apoptosis, senescence and differentiation. Particularly in human leukemia, chromosomal translocations involving crucial hematopoietic transcription factors are frequently causally linked to the disease. Transcription factors commonly have a modular structure, comprising distinct domains for DNA- binding, Read More