PT  - JOURNAL ARTICLE
AU  - TERANISHI, RYUGO
AU  - TAKAHASHI, TSUYOSHI
AU  - KUROKAWA, YUKINORI
AU  - SAITO, TAKURO
AU  - YAMAMOTO,  KAZUYOSHI
AU  - MOMOSE, KOTA
AU  - YAMASHITA, KOTARO
AU  - TANAKA, KOJI
AU  - MAKINO, TOMOKI
AU  - NAKAJIMA, KIYOKAZU
AU  - EGUCHI, HIDETOSHI
AU  - DOKI, YUICHIRO
TI  - Pimitespib, a Novel Heat Shock Protein 90 Inhibitor, Is Effective in Treating Renal Cell Carcinoma by Anti-angiogenetic Signaling
AID  - 10.21873/anticanres.17154
DP  - 2024 Aug 01
TA  - Anticancer Research
PG  - 3343--3348
VI  - 44
IP  - 8
4099  - http://ar.iiarjournals.org/content/44/8/3343.short
4100  - http://ar.iiarjournals.org/content/44/8/3343.full
SO  - Anticancer Res2024 Aug 01; 44
AB  - Background/Aim: Most clear cell renal cell carcinomas (ccRCCs) have a dysfunctional von Hippel-Lindau tumor suppressor protein (VHL). Hypoxia-inducible factors 1 and 2 alpha (HIF1α and HIF2α) accumulate in ccRCC with dysfunctional VHL and up-regulate the vascular endothelial growth factor (VEGF) pathway and tumor angiogenesis. Recently, pimitespib (PIM), a potent ATP-competitive inhibitor of heat shock protein 90 (HSP90), was developed. PIM down-regulates the expression of HIF, a key protein in ccRCC progression, with anti-angiogenic effects. This study aimed to examine the effectiveness of PIM in ccRCC and the underlying mechanisms. Materials and Methods: The efficacy and mechanism of PIM against ccRCCs was evaluated using ccRCC cell lines. Results: PIM inhibited the VEGFR pathway by down-regulating VEGFR 2, phosphorylated VEGFR 2, and protein levels in downstream signaling pathways. The growth of ccRCC cell lines was inhibited by PIM. Furthermore, PIM inhibits HIF1α, HIF2α, and VEGF expression, suggesting that PIM may suppress angiogenesis in addition to the VEGFR pathway. Conclusion: PIM provides a novel approach for treating ccRCC and holds promise for future clinical strategies. Further in vivo and clinical research is required to elucidate the detailed relationship between the effects of PIM and ccRCC.