RESEARCH HIGHLIGHTS Nature Reviews Urology advance online publication 31 March 2015; doi:10.1038/nrurol.2015.68
PROSTATE CANCER
NEW LIGAND– R E C E P T O R TA R G E T S Researchers in the USA have identified two new ligand–receptor systems that are promising candidates for the development of drugs targeted at human metastatic androgen-independent prostate cancer. Although prostate cancer responds initially to androgen deprivation therapy, it usually progresses and becomes androgen independent, leading to soft tissue and bone metastases. Treatment options for patients whose prostate cancer has progressed in this way are limited, and new therapies are greatly needed. “The lack of clinically relevant prostate cancer models has hampered the discovery of important molecules that permit androgen independence and, therefore, could be used as therapeutic targets,” say Mandelin et al., the authors of the latest study. “Recently, Li et al. developed a novel prostate cancer xenograft model that did not express androgen receptor, grew in castrated SCID mice, and induced robust osteoblastic reactions.” Mandelin and co-workers used this novel prostate cancer xenograft model to perform in vivo phage display to investigate functional receptors expressed on metastatic androgen-independent prostate cancer cells. They identified two peptides—PKRGFQD and SNTRVAP—that were enriched in tumour cells, were shown to target the cell surface of androgenindependent cancer cells in vitro and shown to home to androgen-receptor-null prostate cancer cells in vivo. Using affinity chromatography, Mandelin et al. identified α2-macroglobulin as the receptor for PKRGFQD and GRP78 as the receptor for SNTRVAP. The researchers say that these ligand–receptor systems should be considered for validation against androgen‑independent metastatic tumours. “The peptides identified in this study might lead to breakthroughs in fighting metastatic androgen-independent prostate cancer by enabling drug targeting and nanotechnology-based therapeutic strategies, and might lead to significant advances in the management and therapy of this frequently lethal disease,” conclude the authors. Rebecca Kelsey Original article Mandelin, J. et al. Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer. Proc. Natl Acad. Sci. USA doi:10.1073/pnas.1500128112 Further reading Li, Z. G. et al. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. J. Clin. Invest. 118, 2697–2710 (2008)
NATURE REVIEWS | UROLOGY
ADVANCE ONLINE PUBLICATION © 2015 Macmillan Publishers Limited. All rights reserved
PROSTATE CANCER
NEW LIGAND– R E C E P T O R TA R G E T S Researchers in the USA have identified two new ligand–receptor systems that are promising candidates for the development of drugs targeted at human metastatic androgen-independent prostate cancer. Although prostate cancer responds initially to androgen deprivation therapy, it usually progresses and becomes androgen independent, leading to soft tissue and bone metastases. Treatment options for patients whose prostate cancer has progressed in this way are limited, and new therapies are greatly needed. “The lack of clinically relevant prostate cancer models has hampered the discovery of important molecules that permit androgen independence and, therefore, could be used as therapeutic targets,” say Mandelin et al., the authors of the latest study. “Recently, Li et al. developed a novel prostate cancer xenograft model that did not express androgen receptor, grew in castrated SCID mice, and induced robust osteoblastic reactions.” Mandelin and co-workers used this novel prostate cancer xenograft model to perform in vivo phage display to investigate functional receptors expressed on metastatic androgen-independent prostate cancer cells. They identified two peptides—PKRGFQD and SNTRVAP—that were enriched in tumour cells, were shown to target the cell surface of androgenindependent cancer cells in vitro and shown to home to androgen-receptor-null prostate cancer cells in vivo. Using affinity chromatography, Mandelin et al. identified α2-macroglobulin as the receptor for PKRGFQD and GRP78 as the receptor for SNTRVAP. The researchers say that these ligand–receptor systems should be considered for validation against androgen‑independent metastatic tumours. “The peptides identified in this study might lead to breakthroughs in fighting metastatic androgen-independent prostate cancer by enabling drug targeting and nanotechnology-based therapeutic strategies, and might lead to significant advances in the management and therapy of this frequently lethal disease,” conclude the authors. Rebecca Kelsey Original article Mandelin, J. et al. Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer. Proc. Natl Acad. Sci. USA doi:10.1073/pnas.1500128112 Further reading Li, Z. G. et al. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. J. Clin. Invest. 118, 2697–2710 (2008)
NATURE REVIEWS | UROLOGY
ADVANCE ONLINE PUBLICATION © 2015 Macmillan Publishers Limited. All rights reserved
