Cytotoxic LH-RH analogs powerfully inhibited growth of all three
tumor lines in nude mice; AN-152 was significantly stronger than DOX on Panc-1 and
CFPAC-1 cancers.PCR array showed that cytotoxic LH-RH analog AN-152 affected
the expression of genes associated with cellular migration, invasion, metastasis and
angiogenesis more favorably than DOX, however the changes in gene expression
varied considerably among the three cancer lines. Cytotoxic LH-RH analog, AEZS-
108, may be a useful agent for the treatment of LH-RH receptor positive advanced
pancreatic carcinoma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742835/
For example, cytotoxic compounds, such as chlorambucil (Chl), melphalan (Mel), and metal complex related to the cytotoxic complexes cisplatin were coupled with an LHRH analogue to increase their cytotoxic activity against LHRH overexpressing cancer cells. Others used the similar strategy to conjugate cytotoxic drugs such as anthraquinone and methotrexate with LHRH agonist [D-Lys6] and demonstrated enhanced anti-tumor effect compared to the cytotoxic drugs alone.These agents successfully inhibited prostate tumor growth. AN-152 (now called AEZS-108) is one of the best examples of such a strategy. This analogue contains doxorubicin coupled with theLHRH agonist [D-Lys(6)]LHRH. It has shown some promising results, and phase II studies are in progress for their use in castrationresistant prostate cancer. Because of promising results in earlier phases, targeted chemotherapy using LHRH-linked analogues, like AEZS-108, is scheduled to enter phase III studies in advanced endometrial tumors that are positive for LHRH receptor. In addition, deslorelin-docetaxel analogues were also developed and showed 15-fold higher potency than docetaxel alone at 72 h in LNCaP and androgen-independent PC-3 cell lines
