GHRH-receptor as a new targetable biomarker in breast cancer and its correlation with ER/PR/HER2 status.

Nadji, Mehrdad; Block, Norman L.; Lara, Jonathan F.; Michaelson, Richard A.; Pulinthanathu, Rajiv; Tortora, Matthew; Ali, Suhail M.; Leitzel, Kim; Rizvi, Syed A.; Al-Marrawi, Mhd Yaser; Lipton, Allan

doi:10.1200/jco.2015.33.15_suppl.576

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“…VIP and GHRH receptors and their splice variants (SVs) are overexpressed in numerous cancer cells. ,, For that reason, VIP and GHRH receptor antagonists have been explored against different cancers with positive results, their activity being even improved in combination with antitumoral drugs. A different approach has taken advantage of the overexpression of these receptors by combining the peptides with antitumoral formulations, in this case the peptide being the drug carrier .…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers

et al. 2019

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The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration. Also, the dendriplexes were not toxic for no tumoral prostate cells (RPWE-1) or fibroblasts. The use of labeled GHRH peptide (rhodamine labeled) and a dendrimer (fluorescein labeled) allowed us to observe that both systems reach the intracellular milieu after dendriplex formation. The treatment of PC3 cells with the nanoplexes reduced expression of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP). Molecular modeling analysis highlights the important contribution of the carbosilane framework in the stabilization of the dendriplex, since dendrimer interacts with a peptide region where hydrophobic amino acids are presented.

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