ERBB2 and breast carcinoma: In breast cancer cells, NK1 receptors, stimulated by SP, activate secretory pathways that increase extracellular activity of metalloproteinases (MMPs); turning on HER2 growth factor receptor transactivation which, via Src, elicits proliferative and invasive processes.220,221 In fact, cancer cells activate autocrine circuits by releasing SP, and in a preclinical tumor model with breast cancer cells (MDA-MB-231 and MDA-MB-453), NK1 antagonist (L-733,060) inhibits the tumor growth and synergizes with anti-HER2 therapies (AG825, AG1478 or lapatinib inhibitors)176 (Fig. 3).