Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F22%3A00556526" target="_blank" >RIV/67985904:_____/22:00556526 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/22:00556526 RIV/68378050:_____/22:00556526 RIV/67985823:_____/22:00556526 RIV/00064165:_____/22:10450733 RIV/00216208:11310/22:10450733
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/ctm2.645" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/ctm2.645</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ctm2.645" target="_blank" >10.1002/ctm2.645</a>
Alternative languages
Result language
angličtina
Original language name
Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical and Translational Medicine
ISSN
2001-1326
e-ISSN
2001-1326
Volume of the periodical
12
Issue of the periodical within the volume
3
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
e645
UT code for WoS article
000774832800001
EID of the result in the Scopus database
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