Checkpoint kinase 1 inhibitor + low-dose hydroxyurea efficiently kills BRAF inhibitor- and immune checkpoint inhibitor-resistant melanomas
- Author(s)
- Zeng, Z; Ngo, HL; Proctor, M; Rizos, H; Dolcetti, R; Cruz, JG; Wells, JW; Gabrielli, B;
- Details
- Publication Year 2024-01,Volume 37,Issue #1,Page 45-50
- Journal Title
- Pigment Cell & Melanoma Research
- Publication Type
- Research article
- Abstract
- Treatment of melanomas with targeted and immunotherapies has proven effective, but resistance to both treatments is a common outcome leaving a high proportion of patients without effective alternative treatment options. Replication stress is a common feature of melanomas, and this is effectively targeted using a combination of checkpoint kinase 1 (CHK1) inhibitor and low-dose hydroxyurea (LDHU). This combination also promotes inflammatory and anti-tumour immune responses in vivo. Melanoma cell lines resistant to BRAF inhibitor (BRAFi) or immune checkpoint inhibitors (ICI) retain their sensitivity to CHK1i + LDHU, with sensitivity similar to that of parental tumours. In vivo, BRAFi-resistant and BRAFi-sensitive parental tumours produce an identical immune response with treatment.
- Publisher
- Wiley
- Keywords
- Humans; *Melanoma/pathology; Hydroxyurea/pharmacology/therapeutic use; Proto-Oncogene Proteins B-raf; Checkpoint Kinase 1/therapeutic use; Immune Checkpoint Inhibitors/therapeutic use; Drug Resistance, Neoplasm; Protein Kinase Inhibitors/pharmacology/therapeutic use; Cell Line, Tumor; CHK1 inhibitor; immune response; replication stress; treatment resistance
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1111/pcmr.13120
- Open Access at Publisher's Site
https://doi.org/10.1111/pcmr.13120- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-02-22 12:18:53
Last Modified: 2024-02-22 12:19:18