New protein kinase inhibitors in breast cancer: afatinib and neratinib

Abstract

HER2-targeted therapies have been widely used and greatly improved the outcome of HER2-positive breast cancer. Despite the accelerated advancement in recent years, several crucial questions remain unanswered, such as how to treat a prior resistance or affect a sanctuary site, that is, CNS metastasis. The novel next-generation TKIs, afatinib and neratinib, were rationally designed to overcome the resistance by targeting multiple HER family members and irreversibly binding the targets. In spite of the encouraging results of the afatinib and neratinib monotherapies, they have not been proven more efficacious in the combination therapies yet, even though multicenter international trials are still ongoing. The key tasks in the future are to study resistance pathways, design novel strategies to more efficiently test combinations for synergistic effects and identify biomarkers and novel imaging tools to guide individualized therapies.

Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer

“…Preclinical data shows that treatment of athymic nude mice bearing xenografts of various tumors with canertinib results in a significant suppression of tumor growth [23, 27]. Similarly, afatinib (BIBW2992) is another irreversible pan-EGFR inhibitor that has been shown to be effective in inhibiting the tumor growth of lung and breast cancer, both in vitro and in vivo [28-30]. …”

The Impact of Radiation Therapy, Lymph Node Dissection, and Hormonal Therapy on Outcomes of Tissue Expander–Implant Exchange in Prosthetic Breast Reconstruction

“…[9][10][11][12][13][14][15] Furthermore, approximately 15 to 20 percent of breast cancers have amplification of the human epidermal growth factor receptor-2 (HER-2) gene, which plays a role in epithelial cell mitosis, invasion, and antiapoptosis. 16,17 Trastuzumab (Herceptin; Genentech, South San Francisco, Calif.) is a fully humanized monoclonal antibody developed to target the extracellular domain of HER-2 and is widely used in patients with HER-2-positive breast cancer. 17,18 Patients treated with trastuzumab may receive ongoing infusions for up to 12 months, which can coincide with the timing of tissue expander-implant exchange in patients who have undergone immediate prosthetic breast reconstruction.…”

“…16,17 Trastuzumab (Herceptin; Genentech, South San Francisco, Calif.) is a fully humanized monoclonal antibody developed to target the extracellular domain of HER-2 and is widely used in patients with HER-2-positive breast cancer. 17,18 Patients treated with trastuzumab may receive ongoing infusions for up to 12 months, which can coincide with the timing of tissue expander-implant exchange in patients who have undergone immediate prosthetic breast reconstruction.…”

Effect of cycloxygenase-2 silencing on the malignant biological behavior of MCF-7 breast cancer cells

“…Studies of molecular tumor biology have identified that breast cancer is a genetic disease. The activation of oncogenes and the inactivation of tumor suppressor genes in the regulation of the cellular physiological processes leads not only to abnormal cell proliferation and differentiation, but also to defective apoptosis and drug resistance (8,9). Therefore, it is of great importance for the prevention and treatment of breast cancer to identify novel targets for breast cancer gene therapy (5,10).…”