Evidence map›Paper›PMID 32506263›Full record

ArticleCancer immunology, immunotherapy : CII2020

Combination of cyclin-dependent kinase and immune checkpoint inhibitors for the treatment of bladder cancer.

Qilai Long, Ai-Hong Ma, Hongyong Zhang, Zhixiu Cao, Roger Xia, Tzu-Yin Lin, Guru P Sonpavde, Ralph de Vere White, Jianming Guo, Chong-Xian Pan

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. CDK4/6 Inhibition Induces CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Preclinical Models for Bladder Cancer Research.Hematology/oncology clinics of North America · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Qilai LongDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Ai-Hong MaDepartment of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Hongyong ZhangDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Zhixiu CaoDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Roger XiaDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Tzu-Yin LinDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Guru P SonpavdeLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ralph de Vere WhiteDepartment of Urology, University of California Davis Cancer Center, Sacramento, CA, 95817, USA.
Jianming GuoDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. guo.jianming@zs-hospital.sh.cn.
Chong-Xian PanDivision of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA. Chongxian_pan@hms.harvard.edu.ORCID http://orcid.org/0000-0002-8588-3994
University of California, Davis · USSun Yat-sen University · CNDana-Farber Cancer Institute · USHXI (United States) · USWuhan University · CN

Funding

University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health DisparitiesU54CA233306 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CARVAJAL CARMONA, LUIS GUILLERMO, CHEN, MOON SHAO-CHUANG · 2018 to 2022
$6.8M
Targeted-and timed-releasing nanotherapeutics against leukemia stem cellsR01CA176803 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PAN, CHONG-XIAN · 2015 to 2019
$1.8M
Development of targeting nanotherapeutics against bladder cancerI01BX001784 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI PAN, CHONG-XIAN · 2014 to 2017
–
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancerI01BX003840 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI PAN, CHONG-XIAN · 2018 to 2021
–
BLRD VA I01 BX001784BLRD VA I01 BX003840NCI NIH HHS 1R01CA176803-01NCI NIH HHS 1 U54 CA233306NCI NIH HHS R01 CA176803NCI NIH HHS U54 CA233306U.S. Department of Veterans Affairs 1I01 BX003840
6 · The paper itself

Abstract

backgroundPerturbation of the CDK4/6 pathway is frequently observed in advanced bladder cancer. We investigated the potential of targeting this pathway alone or in combination with chemotherapy or immunotherapy as a therapeutic approach for the treatment of bladder cancer

methodsThe genetic alterations of the CDK4/6 pathway in bladder cancer were first analyzed with The Cancer Genome Atlas database and validated in our bladder cancer patient-derived tumor xenografts (PDXs). Bladder cancer cell lines and mice carrying PDXs with the CDK4/6 pathway perturbations were treated with a CDK4/6 inhibitor palbociclib to determine its anticancer activity and the underlying mechanisms. The combination index method was performed to assess palbociclib and gemcitabine drug-drug interactions. Syngeneic mouse bladder cancer model BBN963 was used to assess whether palbociclib could potentiate anti-PD1 immunotherapy.

resultsOf the 413 bladder cancer specimens, 79.2% harbored pertubations along the CDK4/6 pathway. Palbociclib induced G0/G1 cell cycle arrest but with minimal apoptosis in vitro. In mice carrying PDXs, palbociclib treatment reduced tumor growth and prolonged survival from 14 to 32 days compared to vehicle only controls (p = 0.0001). Palbociclib treatment was associated with a decrease in Rb phosphorylation in both cell lines and PDXs. Palbociclib and gemcitabine exhibited antagonistic cytotoxicity in vitro (CI > 3) and in vivo, but palbociclib significantly enhanced the treatment efficacy of anti-PD1 immunotherapy and induced CD8+ T lymphocyte infiltration in syngeneic mouse models.

conclusionsThe CDK4/6 pathway is feasible as a potential target for the treatment of bladder cancer, especially in combination with immunotherapy. A CDK4/6 inhibitor should not be combined with gemcitabine.

Indexed as

Urinary Bladder NeoplasmsAnimalsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell ProliferationCell SurvivalCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DeoxycytidineGemcitabineHumansMicePiperazinesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsAntineoplastic Agents, ImmunologicalCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DeoxycytidineGemcitabinepalbociclibPiperazinesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsPyridinesBladder cancerCDK4/6ChemotherapyImmunotherapyPatient-derived xenograftTargeted therapy

Identifiers

PMID32506263
PMCPMC7572640
OpenAlexW3034126431

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.