scholarly journals Signal Transduction Pathways in Breast Cancer – Drug Targets and Challenges

10.5772/23855 ◽  
2011 ◽  
Author(s):  
Samar Azab ◽  
Ayman Al-Hendy
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Drug Targets ◽  
Cancer Drug ◽  
Signal Transduction Pathways

scholarly journals Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways

2020 ◽  
Vol 295 (50) ◽  
pp. 16906-16919
Author(s):  
Jae-Hong Kim ◽  
Yeojin Seo ◽  
Myungjin Jo ◽  
Hyejin Jeon ◽  
Young-Seop Kim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Migration ◽  
Intracellular Signaling ◽  
Mammalian Cells ◽  
Drug Targets ◽  
Large Scale ◽  
Genetic Interaction ◽  
Genetic Interactions ◽  
Signal Transduction Pathways ◽  
Global View

Kinases are critical components of intracellular signaling pathways and have been extensively investigated with regard to their roles in cancer. p21-activated kinase-1 (PAK1) is a serine/threonine kinase that has been previously implicated in numerous biological processes, such as cell migration, cell cycle progression, cell motility, invasion, and angiogenesis, in glioma and other cancers. However, the signaling network linked to PAK1 is not fully defined. We previously reported a large-scale yeast genetic interaction screen using toxicity as a readout to identify candidate PAK1 genetic interactions. En masse transformation of the PAK1 gene into 4,653 homozygous diploid Saccharomyces cerevisiae yeast deletion mutants identified ∼400 candidates that suppressed yeast toxicity. Here we selected 19 candidate PAK1 genetic interactions that had human orthologs and were expressed in glioma for further examination in mammalian cells, brain slice cultures, and orthotopic glioma models. RNAi and pharmacological inhibition of potential PAK1 interactors confirmed that DPP4, KIF11, mTOR, PKM2, SGPP1, TTK, and YWHAE regulate PAK1-induced cell migration and revealed the importance of genes related to the mitotic spindle, proteolysis, autophagy, and metabolism in PAK1-mediated glioma cell migration, drug resistance, and proliferation. AKT1 was further identified as a downstream mediator of the PAK1-TTK genetic interaction. Taken together, these data provide a global view of PAK1-mediated signal transduction pathways and point to potential new drug targets for glioma therapy.

scholarly journals Strategies to enhance radiosensitivity in breast cancer

2008 ◽  
Vol 11 (8) ◽  
Author(s):  
S. C. Formenti
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Normal Tissue ◽  
Tumor Response ◽  
Signal Transduction Pathways ◽  
Intrinsic Properties ◽  
Host Interactions ◽  
Radiation Treatments ◽  
The Individual ◽  
Effective Radiation

AbstractRadiotherapy is an important component in the treatment of breast cancer. However, the individual tumor response to radiation is variable, reflecting both the intrinsic properties of the tumor and its microenvironment as well as the different, inherited sensitivity of the patient's normal tissue when exposed to the effect of ionizing radiation. These differences have inspired research to discover the underlying signal transduction pathways and to understand when they pertain to the tumor, the host or both. In fact, understanding the mechanisms underlying radiosensitivity of breast cancer not only does it permit to design more effective radiation treatments, but it sheds light on the complexities of tumor-host interactions in this disease.

scholarly journals The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer landscapes

2015 ◽  
Vol 22 (6) ◽  
pp. T161-T176 ◽  
Author(s):  
Amulya Sreekumar ◽  
Kevin Roarty ◽  
Jeffrey M Rosen
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Drug Targets ◽  
Cell Types ◽  
Mammary Development ◽  
Lineage Tracing ◽  
Mammary Epithelial ◽  
Cancer Drug ◽  
Mammary Stem ◽  
Stem Cell Hierarchy

The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage-tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types and the signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective.

Recent Progress and Development of Small Molecule Kinase Inhibitors for the Treatment of Breast Cancer

2020 ◽  
Vol 16 (1) ◽  
pp. 4-19 ◽  
Author(s):  
Debasis Das ◽  
Jian Hong
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cancer Therapy ◽  
Recent Progress ◽  
Kinase Inhibitors ◽  
Signal Transduction Pathways ◽  
Targeted Drugs ◽  
Breast Cancer Therapy ◽  
Health Burden ◽  
Treat Breast Cancer

Breast cancer, the most common health burden to women globally, is considered a major cause of death for women every year. Many signal transduction pathways can cause breast cancer. The kinase inhibitors can interrupt the signaling pathways, minimize tumor growth and consequently cure the disease. The scientists have discovered many kinase inhibitors as targeted drugs for breast cancer. In recent years, the inhibitors of EGFR, HER2, VEGFR, PI3K, CDK4/6, PARP and hormone receptor have been studied well for curing breast cancer. The FDA has approved a few kinase drugs such as trastuzumab, lapatinib, neratinib, palbociclib, abemaciclib, alpelisib to treat breast cancer recently. In this review, we summarized the latest development of kinase inhibitors as breast cancer therapy.

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