PMID- 38090281
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231213
IS  - 1179-1314 (Print)
IS  - 1179-1314 (Electronic)
IS  - 1179-1314 (Linking)
VI  - 15
DP  - 2023
TI  - The Potent Novel CDK4/6 Inhibitor TQB3616 in Hormone Receptor Positive Breast 
      Cancer: Preclinical Characterization with in vitro and Human Tumor Xenograft 
      Models.
PG  - 899-912
LID - 10.2147/BCTT.S434973 [doi]
AB  - PURPOSE: Inhibition of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) 
      pathway exerts a considerable inhibitory effect, preventing the spread and 
      metastasis of breast cancer cells and promoting tumor regression. In this study, 
      we examined the antitumor activity of TQB3616, a novel inhibitor of CDK4/6 
      activity, which showed a greater efficacy improvement in antitumor effects. 
      METHODS: TQB3616 group, abemaciclib group and endocrine or HER-2 targeted 
      combination therapy group were set up respectively. The effects of drugs on cell 
      proliferation activity, cell cycle, apoptosis, downstream protein expression and 
      gene expression of HR positive (T47D, MCF-7) and HER-2 positive (BT474, 
      MDA-MB-361) breast cancer cell lines were studied. The antiproliferative effect 
      of TQB3616 was also measured in vivo. RESULTS: TQB3616 showed a remarkable 
      inhibitory effect on the proliferation of hormone receptor-positive breast cancer 
      cells in vitro. In addition, TQB3616 combined with endocrine therapy or Human 
      Epidermal Growth Factor Receptor 2 (HER2) targeted therapy showed significant 
      synergistic antitumor activity in estrogen receptor (ER)-positive/HER2-negative 
      or HER2-positive breast cancer. In contrast to abemaciclib, which targets the 
      CDK4/6 pathway with proven efficacy, the oral agent TQB3616 not only induced G1 
      stalling, leading to a profound reduction in the level of RB protein 
      phosphorylated at Ser807/811, but also showed enhanced tumor killing effects by 
      promoting cell apoptosis. Oral administration of TQB3616 showed more potent 
      antitumor activity than abemaciclib in an in vitro breast cancer xenograft model, 
      causing significant tumor regression associated with sustained target inhibition 
      in tumor tissue and manageable in vivo toxicity. CONCLUSION: The results of this 
      study indicate that TQB3616 is a novel CDK4/6 inhibitor, and its highly effective 
      antitumor activity against breast cancer is expected to yield promising 
      therapeutic effects in clinical studies.
CI  - (c) 2023 Hu et al.
FAU - Hu, Wenyu
AU  - Hu W
AUID- ORCID: 0000-0003-4793-2131
AD  - Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force 
      Military Medical University, Xi'an, Shaanxi, People's Republic of China.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force 
      Military Medical University, Xi'an, Shaanxi, People's Republic of China.
FAU - Luo, JiaLing
AU  - Luo J
AD  - Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force 
      Military Medical University, Xi'an, Shaanxi, People's Republic of China.
FAU - Zhang, Jian
AU  - Zhang J
AD  - The State Key Laboratory of Cancer Biology, Department of Biochemistry and 
      Molecular Biology, Air Force Military Medical University, Xi'an, Shaanxi, 
      People's Republic of China.
FAU - Li, Nanlin
AU  - Li N
AUID- ORCID: 0000-0002-8762-9439
AD  - Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Air Force 
      Military Medical University, Xi'an, Shaanxi, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20231208
PL  - New Zealand
TA  - Breast Cancer (Dove Med Press)
JT  - Breast cancer (Dove Medical Press)
JID - 101591856
PMC - PMC10715022
OTO - NOTNLM
OT  - CDK inhibitors
OT  - abemaciclib
OT  - apoptosis
OT  - breast cancer
OT  - endocrine therapy
COIS- The authors report no conflicts of interest in this work.
EDAT- 2023/12/13 18:42
MHDA- 2023/12/13 18:43
PMCR- 2023/12/08
CRDT- 2023/12/13 13:07
PHST- 2023/08/11 00:00 [received]
PHST- 2023/11/26 00:00 [accepted]
PHST- 2023/12/13 18:43 [medline]
PHST- 2023/12/13 18:42 [pubmed]
PHST- 2023/12/13 13:07 [entrez]
PHST- 2023/12/08 00:00 [pmc-release]
AID - 434973 [pii]
AID - 10.2147/BCTT.S434973 [doi]
PST - epublish
SO  - Breast Cancer (Dove Med Press). 2023 Dec 8;15:899-912. doi: 10.2147/BCTT.S434973. 
      eCollection 2023.