الفهرس 
Targeted pathways in breast cancerOnly 14 pages are availabe for public view
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Abstract
Excluding skin cancers, breast cancer is the most common malignancy among women, accounting for nearly 1 in 3 cancers diagnosed among women in the United States, and it is the second leading cause of cancer death among women (Howlader et al., 2011).
Despite advances in diagnosis and treatment, breast cancer is the most frequent cause of death in women ages 35 to 55 (Stanley et al., 2010).
Prognosis and survival rate varies greatly depending on cancer type, staging and treatment; 5-year relative survival varies from 98% to 23%, with an overall survival rate of 85 % (Bouganim et al., 2011).
Despite significant advances in early detection and steady progress in the treatment with systemic agents, most breast cancers develop resistance to drugs. Treatment of early-stage breast cancer requires a multimodality approach to eradicate residual cancer and prevent recurrent disease (Lin et al., 2010).
The term targeted therapy refers to drugs that selectively target specific molecular pathways involved in tumor progression. Most of targeted therapies are either small-molecule drugs or monoclonal antibodies (MAbs). Small-molecule drugs are typically able to diffuse into cells and can act on targets that are found inside the cell. While monoclonal antibodies cannot penetrate the cell plasma membrane and are directed against targets that are outside cells or on the cell surface (Sawyers et al., 2004).
Although traditional cytotoxic chemotherapies demonstrate some degree of selectivity by targeting cancer cells that are dividing, they are usually not considered targeted therapy since they are less selective and affect pathways that are common to normal tissues and tumors (Sledge et al., 2005).
The FDA approves the drug trastuzumab (Herceptin) after research shows that adding it to chemotherapy increases survival for women with advanced breast cancer that over-produces a protein called HER2. In 2006, the drug is also approved as part of adjuvant therapy for women with early-stage HER2-positive breast cancer.
Lapatinib (Tykerb) is approved by the FDA for use in combination with capecitabine for patients with advanced breast cancer whose tumors overproduce the HER2 protein.It is used to slow disease progression in cancers that no longer respond to trastuzumab. In 2010, the drug is also approved as an initial therapy in combination with the aromatase inhibitor letrozole (Femara) for patients with HER2-positive cancer (Davidson et al., 2010).
Targeting the pathways that promote or sustain growth and invasion of carcinoma cells is critical to effective treatment of breast cancer. In the past two decades, several monoclonal antibodies and small-molecule inhibitors have been developed and tested in clinical trials that target cancer characteristics such as cell growth, survival, angiogenesis, and metastasis. Several of these targeted agents significantly improved the survival and outcome of the breast cancer patients (Eniu et al., 2007). Such as Epidermal growth factor: EGFR; IGF-1: insulin-like growth factor-I; PI3K: phosphatidylinositol 3-kinase; mTOR: mammalian target of rapamycin; MEK: mitogen-activated protein kinase kinase; VEGF: vascular endothelial growth factor; VEGFR: VEGF receptor; BRAF: B-type RAF kinase; src: v-Src (Rous sarcoma virus) tyrosine kinase; PTEN: phosphatase and tensin homolog; HDAC: histone deacetylases (Burstein et al., 2010).