PMID- 36672355
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230124
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 2
DP  - 2023 Jan 7
TI  - Role of Clock Genes and Circadian Rhythm in Renal Cell Carcinoma: Recent Evidence 
      and Therapeutic Consequences.
LID - 10.3390/cancers15020408 [doi]
LID - 408
AB  - Circadian rhythm regulates cellular differentiation and physiology and shapes the 
      immune response. Altered expression of clock genes might lead to the onset of 
      common malignant cancers, including Renal Cell Carcinoma (RCC). Data from Cancer 
      Genome Atlas (TCGA) indicate that clock genes PER1-3, CRY2, CLOCK, NR1D2 and RORalpha 
      are overexpressed in RCC tissues and correlate with patients' prognosis. The 
      expression of clock genes could finely tune transcription factor activity in RCC 
      and is associated with the extent of immune cell infiltration. The clock system 
      interacts with hypoxia-induced factor-1alpha (HIF-1alpha) and regulates the circadian 
      oscillation of mammalian target of rapamycin (mTOR) activity thereby conditioning 
      the antitumor effect of mTOR inhibitors. The stimulation of natural killer (NK) 
      cell activity exerted by the administration of interferon-alpha, a cornerstone of the 
      first era of immunotherapy for RCC, relevantly varies according to circadian 
      dosing time. Recent evidence demonstrated that time-of-day infusion directly 
      affects the efficacy of immune checkpoint inhibitors in cancer patients. 
      Compounds targeting the circadian clock have been identified and their role in 
      the era of immunotherapy deserves to be further investigated. In this review, we 
      aimed at addressing the impact of clock genes on the natural history of kidney 
      cancer and their potential therapeutic implications.
FAU - Santoni, Matteo
AU  - Santoni M
AD  - Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy.
FAU - Molina-Cerrillo, Javier
AU  - Molina-Cerrillo J
AUID- ORCID: 0000-0003-4616-0598
AD  - Department of Medical Oncology, Hospital Ramon y Cajal, 28029 Madrid, Spain.
FAU - Santoni, Giorgio
AU  - Santoni G
AUID- ORCID: 0000-0003-2757-7064
AD  - Scuola di Scienze del Farmaco e dei Prodotti della Salute, Universita di 
      Camerino, 62032 Camerino, Italy.
FAU - Lam, Elaine T
AU  - Lam ET
AD  - University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
FAU - Massari, Francesco
AU  - Massari F
AUID- ORCID: 0000-0001-6476-6871
AD  - Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via 
      Albertoni-15, 40138 Bologna, Italy.
FAU - Mollica, Veronica
AU  - Mollica V
AD  - Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via 
      Albertoni-15, 40138 Bologna, Italy.
FAU - Mazzaschi, Giulia
AU  - Mazzaschi G
AUID- ORCID: 0000-0003-4019-579X
AD  - Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.
FAU - Rapoport, Bernardo L
AU  - Rapoport BL
AUID- ORCID: 0000-0001-7610-3653
AD  - The Medical Oncology Centre of Rosebank, 129 Oxford Road, Saxonwold, Johannesburg 
      2196, South Africa.
AD  - Department of Immunology, Faculty of Health Sciences, University of Pretoria, 
      Corner Doctor Savage Road and Bophelo Road, Pretoria 0002, South Africa.
FAU - Grande, Enrique
AU  - Grande E
AUID- ORCID: 0000-0002-0134-4732
AD  - Department of Medical Oncology, MD Anderson Cancer Center Madrid, 28033 Madrid, 
      Spain.
FAU - Buti, Sebastiano
AU  - Buti S
AUID- ORCID: 0000-0003-0876-0226
AD  - Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230107
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9856936
OTO - NOTNLM
OT  - HIF
OT  - circadian rhythm
OT  - clock genes
OT  - immunotherapy
OT  - renal cell carcinoma
COIS- E.G. has received honoraria for speaker engagements, advisory roles or funding of 
      continuous medical education from Adacap, AMGEN, Angelini, Astellas, Astra 
      Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, 
      Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, 
      IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring 
      Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre 
      Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho, and Thermo Fisher 
      Scientific. E.G. has received research grants from Pfizer, Astra Zeneca, 
      Astellas, and Lexicon Pharmaceuticals. J.M.-C. declares consultant, advisory or 
      speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen, and BMS; he also 
      received research grants from Pfizer, IPSEN and Roche. The other authors declare 
      no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/22 06:01
PMCR- 2023/01/07
CRDT- 2023/01/21 01:12
PHST- 2022/11/20 00:00 [received]
PHST- 2023/01/03 00:00 [revised]
PHST- 2023/01/05 00:00 [accepted]
PHST- 2023/01/21 01:12 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/22 06:01 [medline]
PHST- 2023/01/07 00:00 [pmc-release]
AID - cancers15020408 [pii]
AID - cancers-15-00408 [pii]
AID - 10.3390/cancers15020408 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Jan 7;15(2):408. doi: 10.3390/cancers15020408.