Interrogating the Involvement of Autophagy, Senescence, and the Immune System in the Actions of Sacituzumab Govitecan as an Anticancer Agent

Antibody-drug conjugates (ADCs) are an emerging class of cancer therapeutics comprised of a tumor-targeting antibody linked to a cytotoxic payload. Sacituzumab govitecan (SG or IMMU-132) is comprised of a trophoblast cell-surface antigen 2 (TROP-2)-directed antibody linked to the topoisomerase 1 inhibitor, SN-38. SG was designed to exploit the overexpression of TROP-2, observed in a variety of different epithelial cancers, to enhance tumor-selective cytotoxicity while minimizing damage to normal tissues. SG is approved for pretreated metastatic triple-negative breast cancer (mTNBC) and hormone receptor-positive human epidermal growth factor receptor 2 (HER2) negative breast cancer patients. While SG has shown significant clinical benefit, the objective response rate (ORR) observed with SG in pretreated mTNBC patients in the Phase I/II basket study was 33.3%, indicating a heterogeneous response profile to SG. This article explores the potential influence of autophagy, senescence, and the patient's immune system on the treatment response.