Additionally exposure to multiple conventional chemotherapeutic agents reduces response rate due to increased efflux of these drugs out of the cells mediated by the overexpression of MDR related efflux pumps or transporters [26]. Therefore, the need for reducing treatment-related RAAS activity toxicity and overcoming MDR leads researchers to explore new classes of target-specific anticancer therapy. 2.2. Combination of Target-Specific Biologic Agent and Small Molecule Chemotherapeutic Agent Small molecule chemotherapeutic Inhibitors,research,lifescience,medical agents lack cancer cell-specific targeting ability and also affect the fast-dividing normal cells of the body (such as blood cells

and the cells lining the mouth, Inhibitors,research,lifescience,medical stomach, and intestines). Therefore, the major adverse effects from these chemotherapeutic agents are nonspecific toxicities including anemia, nausea, vomiting, and hair loss. Biologic

agents are advantageous to chemotherapy in their ability to actively target-specific receptors. Conventional chemotherapy does not discriminate effectively between tumor cells and rapidly dividing normal cells thus leading to nonspecific adverse effects. In contrast, target-specific anticancer therapies interfere with molecular Inhibitors,research,lifescience,medical targets that have an important role in tumor growth or progression distinct from normal cells. Also some of these agents act as inhibitors to MDR-related proteins thereby increasing

the response rate [34]. Overall targeted therapies provide a broader therapeutic window with less toxicity and higher response rate compared to conventional chemotherapy. They are Inhibitors,research,lifescience,medical often useful in combination with chemotherapy (Figure 1(b)) and/or radiation to produce additive or even synergistic effects with unique mechanism of action than traditional cytotoxic therapy. Target-specific anticancer therapeutic agents can be classified by their structures and mechanism of actions as extracellular targeting monoclonal antibodies and intracellular targeting small Inhibitors,research,lifescience,medical molecular tyrosine kinase receptor inhibitors. These agents used in metastatic breast cancer target primarily human epidermal growth factor receptor type 2 (HER2), vascular endothelial growth factor receptor (VEGFR), or epidermal growth factor receptor (EGFR). Currently available target-specific anticancer agent-based combination regimens are listed in Table 2. Table 2 Clinically Rolziracetam used combination regimens of target specific biologic agent(s) in metastatic breast cancer. 2.2.1. Monoclonal Antibody-Based Combination Regimens Monoclonal antibodies are monospecific antibodies made by identical immune cells as clones of a unique parent cell. Due to their nature monoclonal antibodies can be designed to bind to specific substances hence they are widely used for target specific detection or purification [35].