Among patients with hormone receptor (HR)-positive breast cancer, those with residual disease after neoadjuvant chemotherapy have a higher risk of relapse and poorer survival than those with a complete response. Previous studies have revealed a correlation between activation of cell cycle-regulating pathways in HR-positive breast cancer, particularly cyclin-dependent kinase (CDK) 4 and 6/cyclin D1 signaling, and resistance to standard therapies. Although CDK4/6 inhibition by palbociclib in combination with endocrine therapy has shown potent antiproliferative effects in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, the potential role of palbociclib in re-sensitizing chemotherapy-resistant HR-positive breast cancer is not well defined.
View Article and Find Full Text PDFCancer Genomics Proteomics
February 2013
Breast cancer (BC) remains the most common cancer type diagnosed in women. Although targeted therapies have improved patient survival for advanced BC, these tumors frequently relapse due to drug resistance mechanisms. A systems biology approach integrates DNA, RNA and protein alterations generated from multidimensional platforms to better understand the mechanisms that regulate the metastatic process.
View Article and Find Full Text PDFHER-2-positive breast cancers frequently sustain elevated AKT/mTOR signaling, which has been associated with resistance to doxorubicin treatment. Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification.
View Article and Find Full Text PDFWe report the first quantitative and qualitative analysis of the poly (A)⁺ transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor) an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples.
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