Translational Research on Breast Cancer: miRNA, siRNA and Immunoconjugates in Conjugation with Nanotechnology for Clinical Studies

Currently, breast cancer is a global public health issue. However, recent progress in phenotyping and expression profiling of human cancers have greatly enhanced the diagnosis and biological classification of several tumors, in particular breast cancers. Despite significant advances in cytotoxic chemotherapy, endocrine therapy and novel targeted agents, metastatic breast cancer remains an incurable disease (Ocana et al., 2006; Ocana & Pandiella, 2008). The lack of curative potential is partially explained by the heterogeneous biology of this disease which exhibits both de novo and acquired resistance to many treatment modalities (Ocana & Pandiella, 2008). Breast cancers are classified into distinct subtypes using microarray-based gene expression signatures identification; these are largely based on their (Estrogen) ER, progesterone (PR), and HER2 receptor status (Perou et al., 2000; Sorlie et al., 2001; Sorlie et al., 2006). Subtypes were designated Luminal A, which strongly expressed ER and/or PR, but not HER2; Luminal B, which were ER, PR and HER2 positive; Basal tumors which were ER, PR, and HER negative, preferentially affecting young women and women of African origin, usually of high histological grade and more aggressive clinical behavior (Yehiely et al., 2006) . Genomic tumor profiling has provided us with important insights to mechanisms of tumorigenesis and translational data for clinical advances (Bauer et al.). Relative to some cancer types, there is tremendous genomic information available for breast cancers, which includes tumor DNA copy number (Adelaide et al., 2007; Bergamaschi et al., 2006; Chin et al., 2006; Han et al., 2008; Neve et al., 2006) DNA sequence and mutations (Leary et al., 2008; Nikolsky et al., 2008; Shah et al., 2009; Sjoblom et al., 2006; Stephens et al., 2009; Wood et al., 2007), gene expression and protein profiles(Boyd et al., 2008; Hennessy et al., 2009), as well as epigenetics (Andrews et al.; Ruike et al.) and microRNAs (Iorio et al., 2005a; Mattie et al., 2006a). Promising new targeted agents, such as small molecule tyrosine kinase inhibitors and monoclonal antibodies such as trastuzumab, which targets breast cancer cells