KITAHARA Shuji    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Associate Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Inhibition of CXCR4 Enhances the Efficacy of Radiotherapy in Metastatic Prostate Cancer Models.
Journal	Formal name：Cancers Abbreviation：Cancers (Basel) ISSN code：20726694/20726694
Domestic / Foregin	Foregin
Volume, Issue, Page	15(4),pp.1021
Author and coauthor	GUPTA Nisha†, OCHIAI Hiroki, HOSHINO Yoshinori, KLEIN Sebastian, ZUSTIN Jozef, RAMJIAWAN Rakesh R, KITAHARA Shuji, MAIMON Nir, BAZOU Despina, CHIANG Sarah, LI Sen, SCHANNE Daniel H,, JAIN Rakesh K, MUNN Lance L, HUANG Peigen,, KOZIN Sergey V, DUDA Dan G
Publication date	2023/02
Summary	Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.
DOI	10.3390/cancers15041021
PMID	36831366