Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

INTRODUCTION: Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease. Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.

Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview.

Despite a long history of immunotherapeutic approaches to treatment, most genitourinary malignancies are not cured by existing immunotherapy regimens. More recently, cell surface molecules known as immune checkpoints have become the focus of efforts to develop more effective immunotherapies. Interactions between these molecules and their ligands inhibit the proliferation and function of tumor-specific lymphocytes. A monoclonal antibody blocking 1 of these checkpoints was approved for the treatment of metastatic melanoma and is now being tested in other malignancies. The objective responses seen in these early trials of checkpoint blockade are driving renewed enthusiasm for cancer immunotherapy. There are several ongoing and planned trials in genitourinary malignancies of single-agent inhibitors, as well as combinations targeting multiple checkpoints or adding other types of therapies to checkpoint blockade.

Novel molecular targets for urothelial carcinoma.

INTRODUCTION: Urothelial cancer (UC) remains a significant public health problem, with no new second-line agents FDA-approved in the US. Next-generation sequencing technologies are starting to generate a molecular landscape of UC thus revealing novel molecular targets. AREAS COVERED: In this review, the authors provide a detailed review of novel molecular targets in UC based on published genomic analyses of urothelial tumors. We provide an overview of each molecular target with a brief discussion of therapeutic strategies and clinical trials targeting each pathway. EXPERT OPINION: UC continues to be a lethal disease with no FDA-approved effective second-line therapies. Platinum resistance continues to be a daunting clinical problem. Next-generation sequencing methods have led to the elucidation of numerous molecular targets in UC, including PI3K, to the elucidation of numerous molecular targets in UC, including PI3K, ERBB2 and FGFR3, among many others. These molecular perturbations can be exploited therapeutically with targeted therapies in patient populations enriched for these molecular alterations, thus paving the way for precision medicine in UC management.