Table 1 Summary of therapy targeting brachyury protein in cancer
From: Multiple malignant tumors in a patient with familial chordoma, a case report
Treatment | Mechanism | Disease model | Stage | Result | Ref |
|---|---|---|---|---|---|
Yeast-Based vaccine | Immune stimulation | metastatic or unresectable locally advanced malignant solid tumors | Clinical phase I | Induce T-cell response. No serious adverse effects. PR 10%; SD 80%; PD 10%. Currently ongoing phase II study (NCT02383498) | [50] |
DNA Nanoparticle-Mediated shRNA | shRNA inhibit brachyury expression | Chordoma | Pre-clinical | Induced apoptosis, upregulated the epithelial biomarker, E-cadherin, downregulated the mesenchymal biomarker, Snail and Slug, and suppressed cell growth | [53] |
Poxviral TRICOM-Based Vaccine | Immune stimulation | metastatic or unresectable locally advanced malignant solid tumors | Clinical phase I | Induce T-cell response. No serious adverse effects. SD 45%; PD 55% | [51] |
Afatinib | Brachyury degradation | Chordoma | Pre-clinical | Antitumor efficacy in U-CH1, SF8894, CF322, and CF365 chordoma tumor models in vivo. Currently ongoing phase II study in EGFR expressing chordoma (NCT03083678) and metastatic or unresectable chordoma (EUDRACT 2016-002766-31) | [46] |
THZ1 (CDK 7/12/13 inhibitors) | Down-regulation of brachyury expression | Chordoma | Pre-clinical | Can reduce tumor growth in vivo | [47] |
Modified Vaccinia Ankara Priming Vaccine | Immune stimulation | metastatic or unresectable locally advanced malignant solid tumors | Clinical phase I | Well tolerated and induces immune responses to brachyury. SD 60%; PD 40% | [52] |
H3K27 demethylase inhibitors | Epigenetic silencing of TBXT | Chordoma | Pre-clinical | Pharmacologic inhibition of H3K27-demethylases promotes chordoma cell death | [54] |