Abstract
Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths worldwide. Despite improvements in diagnosis and treatment, new treatment options are urgently needed for advanced stages of the disease. Targeted toxins are chemical conjugates or fully recombinant proteins consisting of a binding domain directed against a target antigen on the surface of cancer cells and a toxin domain, which is transported into the cell for the induction of apoptosis. In the last decades, targeted toxins against prostate cancer have been developed. Several challenges, however, became apparent that prevented their direct clinical use. They comprise immunogenicity, low target antigen binding, endosomal entrapment, and lysosomal/proteasomal degradation of the targeted toxins. Moreover, their efficacy is impaired by prostate tumors, which are marked by a dense microenvironment, low target antigen expression, and apoptosis resistance. In this review, current findings in the development of targeted toxins against prostate cancer in view of effective targeting, reduction of immunogenicity, improvement of intracellular trafficking, and overcoming apoptosis resistance are discussed. There are promising approaches that should lead to the clinical use of targeted toxins as therapeutic alternatives for advanced prostate cancer in the future.
Highlights
Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths worldwide
prostate cancer (PC) is regarded as a suitable target for targeted toxin therapy, because (a) PC cells are generally slowly growing and express well described target antigens, (b) PC metastases predominantly involve lymph nodes and bones, locations that are readily accessible to circulating targeted toxins, and (c) the prostate-specific antigen (PSA)
We found a 7.5- to 19-fold increased cytotoxicity of the anti-prostate specific membrane antigen (PSMA) targeted toxin D7(VL-VH)PE40 after combination with docetaxel on LNCaP and C4-2 cells
Summary
The fight against prostate cancer (PC) is a major challenge. Improvements in diagnosis and treatment in recent years have led to reduced or at least stable mortality rates in most countries [1]. With almost 1.4 million estimated new cases and 375,000 deaths. PC remains the second most frequent cancer and the fifth leading cause of cancer deaths in men worldwide [2]. Primary tumors can be successfully treated by surgery or radiation. Curative treatment is no longer possible in advanced stages and many patients develop castration resistant PC (CRPC) after androgen deprivation therapy. The median survival of patients with metastatic CRPC ranges between 15 and 36 months [3,4]. New treatment options are urgently needed for advanced stages of the disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
