GNRHR expression

We showed that the engineered GnRH-hpRNase1 can specifically target the GnRH receptor-expressing cells and inhibit their proliferation through inducing apoptosis. Owing to its promising anti-tumor activity, the fusion enzyme can be further examined on GnRH-R-expressing tumor xenografts to evaluate its anti-tumor effects in vivo.

Altogether, these data describe a novel role for AXL as a modulator of GnRH receptor signaling. Video Abstract.

Another recent approach based on this knowledge was the use of GnRH peptides for developing specific targeted therapies, improving the delivery and accumulation of drugs in tumoral cells, and decreasing most side effects of current treatments. In this review, we discuss the conventional uses of GnRH analogs, together with the recent advances in GnRH-based drug delivery for ovarian, breast, and prostatic cancer cells.

GnRHR inhibits TNBC proliferation and metastasis, suggesting it could be targeted for TNBC treatment.

Some promising findings from these studies indicate that GnRH receptor targeting is a potential strategy to efficiently guide anticancer therapeutics, diagnostic agents, and nucleic acids directly to cancer cells. Lastly, some limitations of the current research and suggestions for more successful outcomes in clinical trials of these delivery systems are highlighted.

Besides the selective targeting that the specific conjugate could offer, we also recorded high internalization levels in T24 bladder cancer cells. The ruthenium(ii) polypyridyl peptide-based conjugates we developed is an intriguing approach that offers targeted cell imaging in the Near Infrared region, and simultaneously paves the way for further advancements in the dynamic studies on cellular imaging.

This antitumor activity is mainly mediated by the GnRH-R-associated Gαi/cAMP signaling pathway. In this review, we dissect the molecular mechanisms underlying the role of the androgen/AR and GnRH/GnRH-R axes in CRPC progression and the possible therapeutic implications.