Počet záznamů: 1
Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy
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SYSNO ASEP 0556526 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy Tvůrce(i) Štemberková-Hubáčková, Soňa (BTO-N)
Zobalová, Renata (BTO-N) RID
Dubišová, Maria (BTO-N)
Šmigová, J. (CZ)
Dvořáková, Šárka (BTO-N) ORCID
Kořínková, Klára (BTO-N)
Ezrová, Zuzana (BTO-N) ORCID
Endaya, Berwini (BTO-N)
Blažková, Kristýna (BTO-N)
Vlčák, Erik (UMG-J)
Brisudová, Petra (BTO-N)
Le, Dan-Diem Thi (BTO-N)
Juhás, Štefan (UZFG-Y) RID, ORCID
Rosel, D. (CZ)
Kelemen, Daniela Cristina (BTO-N)
Sovilj, Dana (BTO-N)
Vačurová, Eliška (BTO-N) ORCID
Čajka, Tomáš (FGU-C) RID, ORCID, SAI
Filimonenko, Vlada (UMG-J) RID, ORCID
Dong, L. (AU)
Anděra, Ladislav (BTO-N)
Hozák, Pavel (UMG-J) RID, ORCID
Brabek, J. (CZ)
Bielcikova, Z. (CZ)
Štursa, Jan (BTO-N)
Werner, Lukáš (BTO-N)
Neužil, Jiří (BTO-N) RIDCelkový počet autorů 27 Číslo článku e645 Zdroj.dok. Clinical and Translational Medicine. - : Wiley - ISSN 2001-1326
Roč. 12, č. 3 (2022)Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Mitochondrially targeted tamoxifen ; Renal cancer ; Immunotherapy Vědní obor RIV FD - Onkologie a hematologie Obor OECD Pathology CEP GA20-05942S GA ČR - Grantová agentura ČR GX21-04607X GA ČR - Grantová agentura ČR GA18-02550S GA ČR - Grantová agentura ČR GA19-08772S GA ČR - Grantová agentura ČR NU21-03-00195 GA MZd - Ministerstvo zdravotnictví LM2018129 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LTC19048 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LO1609 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF16_013/0001775 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 ; UZFG-Y - RVO:67985904 ; FGU-C - RVO:67985823 UT WOS 000774832800001 DOI 10.1002/ctm2.645 Anotace Mitochondrially targeted tamoxifen (MitoTam) has recently undergone phase 1/1b clinical trial in patients with various solid tumors. Since patients with clear cell renal carcinoma showed the highest response of the tested diagnoses, we studied the effect of MitoTam on renal cancer in vitro and in vivo to reveal its mechanism of action in more detail and to better understand its benefit for patients. Using primarily the murine RenCa renal cancer cell line and the derived syngeneic mouse tumor model, we studied mechanism of MitoTam toxicity including the mode of death, the role of mitochondria in the effects of the agent, and its efficacy in suppressing syngeneic tumors in mice alone and in combination with the immune checkpoint inhibitors (ICIs), monoclonal antibodies blocking PD-1 and PD-L1. Our findings show a complex effect of MitoTam on mitochondrial function and integrity of renal cancer cells. The agent inhibits complex I-dependent respiration and lowers mitochondrial potential, which results in activation of necroptosis as the major mode of cell death. As a consequence, MitoTam reduces growth of renal tumors as well as metastatic spread of tumor cells via specific targeting of malignant tissue in a mouse model. Moreover, combination of MitoTam with immunotherapy to enhance its anti-cancer efficacy shows significantly increased suppression of tumor growth as well as increased survival of experimental animals compared to single agent treatment. Our data provide a mechanistic rationale for testing of both mono and/or combinatorial therapy with MitoTam plus ICIs in renal carcinomas in Phase 2 trial. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2023 Elektronická adresa https://onlinelibrary.wiley.com/doi/10.1002/ctm2.645
Počet záznamů: 1