The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target

Abstract

// David M. Goldenberg 1, 2 , Rhona Stein 1 and Robert M. Sharkey 1, 3 1 Center for Molecular Medicine and Immunology, Belleville, NJ, USA 2 IBC Pharmaceuticals, Inc., Morris Plains, NJ, USA 3 Immunomedics, Inc., Morris Plains, NJ, USA Correspondence to: David M. Goldenberg, email: dmg.gscancer@att.net Keywords: TROP-2; TACSTD2; sacituzumab govitecan; antibody-drug conjugates; immunotherapy Received: April 30, 2018      Accepted: May 31, 2018      Published: June 22, 2018 ABSTRACT TROP-2 is a glycoprotein first described as a surface marker of trophoblast cells, but subsequently shown to be increased in many solid cancers, with lower expression in certain normal tissues. It regulates cancer growth, invasion and spread by several signaling pathways, and has a role in stem cell biology and other diseases. This review summarizes TROP-2’s properties, especially in cancer, and particularly its role as a target for antibody-drug conjugates (ADC) or immunotherapy. When the irinotecan metabolite, SN-38, is conjugated to a humanized anti-TROP-2 antibody (sacituzumab govitecan), it shows potent broad anticancer activity in human cancer xenografts and in patients with advanced triple-negative breast, non-small cell and small-cell lung, as well as urothelial cancers.