PTX-9908

In conclusion, we compared different 177Lu-radiolabelled CXCR4-targeting peptides for their binding potential in GBM, and demonstrated their varied cytotoxic action against GBM cells in vitro, with POL3026 being the most promising, causing considerable DNA damage. Though the peptide's systemic biodistribution remains to be improved, our data demonstrate the potential of [177Lu]Lu-DOTA-POL3026 for CXCR4-TRT in the context of GBM.

CTCE-9908 significantly inhibited melanoma cell survival at a concentration 10 times lower than the IC50 in B16 F10 cells but not RAW 264.7 cells. However, CTCE-9908 did not affect CXCR4 phosphorylation, apoptosis, or cell cycle distribution in either cell line.

Here, we have developed a CXCR4-targeted antitumor peptidomimetic (named CTCE-KLAK), which is a fusion of the CXCR4 receptor antagonist CTCE-9908 and the D-form of proapoptotic peptide (KLAKLAK), for the treatment of breast cancer...In addition, cell death by CTCE-KLAK was not prevented by z-VAD-fmk, a pan-caspase inhibitor that inhibits cisplatin-induced cell death...Intravenous administration of CTCE-KLAK significantly inhibited tumor growth and lung metastasis. Together, these findings suggest that the necrosis-inducing peptidomimetic CTCE-KLAK is a promising CXCR4-targeted agent for treating triple-negative breast cancer.

P1/2, N=50, Recruiting, TCM Biotech International Corp. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

CTCE-9908, a CXCR-4 antagonist derived from human CXCL12, hinders receptor phosphorylation and the subsequent signalling pathways that would be activated...In addition, increased VEGF-C protein levels lead to enhanced CXCR-4 protein expression. Therefore, effective blocking of VEGR-3 and CXCR-4 may inhibit tumour cell metastasis by hampering intracellular proteins promoting adhesion.

For this reason, chemokines receptors represent potential targets for the treatment of cancer growth and metastasis. In this review paper, the role of the CXCL12/CXCR4 signalling pathway in the development of cancer is highlighted together with the current available treatments involving the CTCE-9908 compound in combination with microtubule inhibitors like paclitaxel and docetaxel.