Emerging Targeted Therapies for Breast Cancer

Abstract

Increased understanding of the molecular events involved in cancer development has led to the identification of a large number of novel targets and, in parallel, to the development of multiple approaches to anticancer therapy. Targeted therapy focuses on specific molecules in the malignant cell signal transduction machinery, including crucial molecules involved in cell invasion, metastasis, apoptosis, cell-cycle control, and tumor-related angiogenesis. In breast cancer, two new targeted agents have recently been approved: lapatinib, directed against the human epidermal growth factor receptor 2 (HER2); and bevacizumab, directed against vascular endothelial growth factor (VEGF). Multiple other targeted agents are under evaluation in clinical trials, including inhibitors of the epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, other VEGF or VEGF-receptor inhibitors, and agents that alter crucial signaling pathways, such as RAS/MEK/ERK; phosphatidylinositol-3-kinase/Akt/ mammalian target of rapamycin; insulin-like growth factor/insulin-like growth factor receptor; poly (ADP-ribose) polymerase 1; and others. In this review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with traditional cytotoxic agents.

HIF-1 is involved in the negative regulation of AURKA expression in breast cancer cell lines under hypoxic conditions

“…Advances in molecular characterization of tumor by microarray profiling allowed the identification of five distinct molecular subtypes of BC which have led to the identification of a large number of novel targets and, in parallel, to the development of multiple approaches for anticancer therapy [2,3]. Numerous microarray-based gene expression studies performed on several types of solid tumors revealed significant changes in key genes involved in progression and regulation of the cell cycle [4,5].…”

PET imaging of HER-2-positive tumours

“…Trastuzumab, a humanized monoclonal antibody, improves response rates, time to progression and even survival when used alone or added to chemotherapy in patients with stage IV disease. Moreover, in recent years several targeted agents have become available including lapatinib, a selective, reversible dual inhibitor of the epidermal growth factor receptor (EGFR; HER-1) and HER-2 [2].…”

Targeted Apoptosis in Breast Cancer Immunotherapy

“…The development of breast cancers, like other processes of carcinogenesis, involves uncontrolled cell proliferation and insufficient apoptosis due to either the lack of proapoptotic stimuli in the in vivo environment or the disturbance of cellular apoptotic pathways (Brown & Attardi, 2005). Whereas both chemotherapy and radiation caused massive apoptotic cell death in the tumor tissues, we are far from conquering the breast malignancies until the establishment of targeted pro-apoptotic therapeutic protocols or the development of apoptosis-inducing drugs that target the tumor without causing severe impairment of the normal organism (Alvarez et al, 2010;Fulda & Debatin, 2006;Motyl et al, 2006;Muschel et al, 1998). However, thanks to the elucidation of mechanisms underlying physiological and pathological apoptosis, studies have been addressed in the development of pro-apoptotic strategies targeting the cancer cells, which has provided novel approaches to the successful immutherapy of breast cancers (Schlotter et al, 2008).…”