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Naslov:A phase Ib clinical trial of metformin and chloroquine in patients with IDH1-mutated solid tumors
Avtorji:ID Khurshed, Mohammed (Avtor)
ID Molenaar, Remco J. (Avtor)
ID Linde, Myra E van (Avtor)
ID Mathôt, Ron A (Avtor)
ID Struys, Eduard A. (Avtor)
ID Wezel, Tom van (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
ID Klümpen, Heinz-Josef (Avtor)
ID Bovée, Judith V. M. G. (Avtor)
ID Wilmink, Johanna W (Avtor)
Datoteke:URL URL - Izvorni URL, za dostop obiščite https://www.mdpi.com/2072-6694/13/10/2474
 
.pdf PDF - Predstavitvena datoteka, prenos (3,11 MB)
MD5: 30853BE4A98387F63009427B6A5F9665
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek:Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. Methods: Patients with IDH1-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma received oral combinational treatment with the antidiabetic drug metformin and the antimalarial drug chloroquine. The primary objective was to determine the occurrence of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Radiological and biochemical tumor responses to metformin and chloroquine were investigated using CT/MRI scans and magnetic resonance spectroscopy (MRS) measurements of D-2HG levels in serum. Results: Seventeen patients received study treatment for a median duration of 43 days (range: 7–74 days). Of twelve evaluable patients, 10 patients discontinued study medication because of progressive disease and two patients due to toxicity. None of the patients experienced a DLT. The MTD was determined to be 1500 mg of metformin two times a day and 200 mg of chloroquine once a day. A serum D/L-2HG ratio of ≥4.5 predicted the presence of an IDH1 mutation with a sensitivity of 90% and a specificity of 100%. By utilization of digital droplet PCR on plasma samples, we were able to detect tumor-specific IDH1 hotspot mutations in circulating tumor DNA (ctDNA) in investigated patients. Conclusion: Treatment of advanced IDH1-mutated solid tumors with metformin and chloroquine was well tolerated but did not induce a clinical response in this phase Ib clinical trial.
Ključne besede:metformin, chloroquine, cancer, isocitrate dehydrogenase, pharmacokinetics, glioblastoma, intrahepatic cholangiocarcinoma, chondrosarcoma
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:19.05.2021
Leto izida:2021
Št. strani:str. 1-16
Številčenje:Vol. 13, iss. 10
PID:20.500.12556/DiRROS-19451 Novo okno
UDK:577.2
ISSN pri članku:2072-6694
COBISS.SI-ID:97801987 Novo okno
Opomba:Nasl. z nasl. zaslona; Opis vira z dne 17. 2. 2022;
Datum objave v DiRROS:19.07.2024
Število ogledov:442
Število prenosov:272
Metapodatki:XML DC-XML DC-RDF
:
KHURSHED, Mohammed, MOLENAAR, Remco J., LINDE, Myra E van, MATHÔT, Ron A, STRUYS, Eduard A., WEZEL, Tom van, NOORDEN, Cornelis J. F. van, KLÜMPEN, Heinz-Josef, BOVÉE, Judith V. M. G. in WILMINK, Johanna W, 2021, A phase Ib clinical trial of metformin and chloroquine in patients with IDH1-mutated solid tumors. Cancers [na spletu]. 2021. Vol. 13, no. 10, p. 1–16. [Dostopano 6 april 2025]. Pridobljeno s: https://dirros.openscience.si/IzpisGradiva.php?lang=slv&id=19451
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Gradivo je del revije

Naslov:Cancers
Skrajšan naslov:Cancers
Založnik:MDPI
ISSN:2072-6694
COBISS.SI-ID:517914137 Novo okno

Gradivo je financirano iz projekta

Financer:SNSF - Swiss National Science Foundation
Številka projekta:10460
Naslov:Soziale Situation, sozialmedizinische Orientierungen und Inanspruchnahme medizinischer Dienstleistungen
Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:J3-2526-2020
Naslov:Razkrivanje niše matičnih glioma celic v iskanju novih terapevtskih ciljev pri bolnikih z glioblastomom
Financer:Drugi - Drug financer ali več financerjev
Program financ.:Academic Medical Center
Naslov:PhD Scholarship
Financer:Drugi - Drug financer ali več financerjev
Številka projekta:KWF grant 10460

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

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