PMID- 38327067
OWN - NLM
STAT- MEDLINE
DCOM- 20240209
LR  - 20240311
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 25
IP  - 1
DP  - 2024 Dec 31
TI  - Influence of genetic polymorphisms in vascular endothelial-related genes on the 
      clinical outcome of axitinib in patients with metastatic renal cell carcinoma.
PG  - 2312602
LID - 10.1080/15384047.2024.2312602 [doi]
LID - 2312602
AB  - OBJECTIVE: Axitinib is an oral multi-target tyrosine kinase inhibitor used for 
      the treatment of renal cell carcinoma (RCC). Because of the severe adverse events 
      (AEs) associated with axitinib, patients often need dose reductions or 
      discontinue its use, highlighting the need for effective biomarkers to assess 
      efficacy and/or AEs. The aim of this study was to investigate the relationship 
      between single nucleotide polymorphisms (SNPs) in genes involved in the 
      pharmacodynamic action of axitinib and clinical prognosis and AEs in metastatic 
      RCC (mRCC) patients. METHODS: This study included 80 mRCC patients treated with 
      first-, second-, or third-line axitinib (5 mg orally twice daily). Clinical 
      parameters and genetic polymorphisms were examined in 75 cases (53 males and 22 
      females). We assessed three SNPs in each of three candidate genes namely, 
      angiotensin-converting enzyme (ACE), nitric oxide synthase 3 (NOS3), and 
      angiotensin II receptor type 1 (AT1R), all of which are involved in axitinib 
      effects on vascular endothelial function. RESULTS: Axitinib-treated patients 
      carrying the ACE deletion allele suffered more frequently from hand-foot syndrome 
      and a deterioration in kidney function (p  = .045 and p =  0.005, respectively) 
      whereas those carrying the NOS3 G allele suffered more frequently from 
      proteinuria and multiple AEs (p  = .025 and p =  0.036, respectively). 
      CONCLUSIONS: Our study found that the ACE deletion allele and the NOS3 G allele 
      are associated with increased AEs.
FAU - Numakura, Kazuyuki
AU  - Numakura K
AUID- ORCID: 0000-0002-5899-1738
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Igarashi, Ryoma
AU  - Igarashi R
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Takahashi, Makoto
AU  - Takahashi M
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Nara, Taketoshi
AU  - Nara T
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Kanda, Sohei
AU  - Kanda S
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Saito, Mitsuru
AU  - Saito M
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Narita, Shintaro
AU  - Narita S
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Inoue, Takamitsu
AU  - Inoue T
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Niioka, Takenori
AU  - Niioka T
AD  - Department of Pharmacy, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Miura, Masatomo
AU  - Miura M
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Habuchi, Tomonori
AU  - Habuchi T
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240207
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - C9LVQ0YUXG (Axitinib)
RN  - 0 (Indazoles)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Humans
MH  - Male
MH  - Female
MH  - Axitinib/adverse effects
MH  - *Carcinoma, Renal Cell/drug therapy/genetics
MH  - *Kidney Neoplasms/drug therapy/genetics/pathology
MH  - Indazoles/adverse effects
MH  - Polymorphism, Single Nucleotide
MH  - *Antineoplastic Agents/therapeutic use
PMC - PMC10857686
OTO - NOTNLM
OT  - ACE
OT  - NOS3
OT  - Renal cell carcinoma
OT  - axitinib
OT  - polymorphisms
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2024/02/08 06:43
MHDA- 2024/02/09 06:42
PMCR- 2024/02/07
CRDT- 2024/02/08 02:14
PHST- 2024/02/09 06:42 [medline]
PHST- 2024/02/08 06:43 [pubmed]
PHST- 2024/02/08 02:14 [entrez]
PHST- 2024/02/07 00:00 [pmc-release]
AID - 2312602 [pii]
AID - 10.1080/15384047.2024.2312602 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2024 Dec 31;25(1):2312602. doi: 10.1080/15384047.2024.2312602. 
      Epub 2024 Feb 7.