Targeting GPNMB with glembatumumab vedotin: Current developments and future opportunities for the treatment of cancer

GPNMB has emerged as an immunomodulator and an important positive mediator of tumor progression and metastasis in numerous solid cancers. Tumor intrinsic GPNMB-mediated effects on cellular signaling, coupled with the ability of GPNMB to influence the primary tumor and metastatic microenvironments in a non-cell autonomous fashion, combine to augment malignant cancer phenotypes. In addition, GPNMB is often overexpressed in a variety of cancers, making it an attractive therapeutic target. In this regard, glembatumumab vedotin, an antibody-drug conjugate (ADC) that targets GPNMB, is currently in clinical trials as a single agent in multiple cancers. In this review, we will describe the physiological functions of GPNMB in normal tissues and summarize the processes through which GPNMB augments tumor growth and metastasis. We will review the pre-clinical and clinical development of glembatumumab vedotin, evaluate on-going clinical trials, explore emerging opportunities for this agent in new disease indications and discuss exciting possibilities for this ADC in the context of combination therapies.