HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments

Abstract : Clear cell Renal Cell (RCC) and Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a pro-angiogenic/pro-inflammatory context. Despite conventional or targeted therapies, metastatic RCC and HNSCC remain incurable. Alternative treatments to reference therapies (sunitinib, a multi tyrosine kinase inhibitor for RCC or cisplatin for HNSCC) are urgently needed on relapse. Here, we described the relevance of targeting the ELR+CXCL cytokines receptors, CXCR1/2, for the treatment of these two cancer types. Methods: The relevance to patient treatment was evaluated by correlating the ELR+CXCL/CXCR1/2 levels to survival using online available data. We report herein the synthesis of new pharmacological inhibitors of CXCR1/2 with anti-proliferation/survival activity. The latter was evaluated with the XTT assay with leukemic, breast, RCC and HNSCC cell lines. Their relevance as an alternative treatment was tested on sunitinib- and cisplatin- resistant cells. The most efficient compound was then tested in a mouse model of RCC and HNSCC. Results: RCC and HNSCC expressed the highest amounts of CXCR1/2 of all cancers. High levels of ELR+CXCL cytokines (CXCL1, 2, 3, 5, 6, 7, 8) correlated to shorter survival. Among the 33 synthesized and tested molecules, compound C29 reduced ELR+CXCL/CXCR1/2-dependent proliferation and migration of endothelial cells. C29 exerted an anti-proliferation/survival activity on a panel of cancer cells including naive and resistant RCC and HNSCC cells. C29 reduced the growth of experimental RCC and HNSCC tumors by decreasing tumor cell proliferation, angiogenesis and ELR+/CXCL-mediated inflammation. Conclusion: Our study highlights the relevance of new CXCR1/2 inhibitors for the treatment of RCC or HNSCC as first-line treatment or at relapse on reference therapies.
Complete list of metadata

Cited literature [43 references]  Display  Hide  Download

https://hal-cnam.archives-ouvertes.fr/hal-02308756
Contributor : Aurélie Puybonnieux Connect in order to contact the contributor
Submitted on : Tuesday, October 8, 2019 - 4:56:21 PM
Last modification on : Wednesday, March 16, 2022 - 3:47:22 AM

File

thnov09p5332.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Maeva Dufies, Oleksandr Grytsai, Cyril Ronco, Oumar Camara, Damien Ambrosetti, et al.. New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments. Theranostics, Ivyspring International Publisher, 2019, 9 (18), pp.5332-5346. ⟨10.7150/thno.34681⟩. ⟨hal-02308756⟩

Share

Metrics

Record views

225

Files downloads

92