RT Journal Article
SR Electronic
T1 Pimitespib, a Novel Heat Shock Protein 90 Inhibitor, Is Effective in Treating Renal Cell Carcinoma by Anti-angiogenetic Signaling
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3343
OP 3348
DO 10.21873/anticanres.17154
VO 44
IS 8
A1 TERANISHI, RYUGO
A1 TAKAHASHI, TSUYOSHI
A1 KUROKAWA, YUKINORI
A1 SAITO, TAKURO
A1 YAMAMOTO,  KAZUYOSHI
A1 MOMOSE, KOTA
A1 YAMASHITA, KOTARO
A1 TANAKA, KOJI
A1 MAKINO, TOMOKI
A1 NAKAJIMA, KIYOKAZU
A1 EGUCHI, HIDETOSHI
A1 DOKI, YUICHIRO
YR 2024
UL http://ar.iiarjournals.org/content/44/8/3343.abstract
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.