Evidence map›Paper›PMID 30236142›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma.

Cheng-Lung Hsu, Kar-Wai Lui, Lang-Ming Chi, Yung-Chia Kuo, Yin-Kai Chao, Chun-Nan Yeh, Li-Yu Lee, Yenlin Huang, Tung-Liang Lin, Mei-Yuan Huang and 12 more

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

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 36 citations in OpenAlex.

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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

22 authors at 3 institutions in 1 country.

Cheng-Lung HsuDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Kar-Wai LuiDepartment of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Lang-Ming ChiClinical Proteomics Core Laboratory, Chang Gung Memorial Hospital, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Yung-Chia KuoDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Yin-Kai ChaoDivision of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Chun-Nan YehDepartment of General Surgery, Liver Research Center, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Li-Yu LeeDepartment of Pathology, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Yenlin HuangDepartment of Pathology, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Tung-Liang LinDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Mei-Yuan HuangDepartment of Microbiology and Immunology, Molecular Medicine Research Center, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Lin-Kou, Taoyuan, 333, Taiwan, Republic of China.
Yi-Ru LaiDepartment of Microbiology and Immunology, Molecular Medicine Research Center, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Lin-Kou, Taoyuan, 333, Taiwan, Republic of China.
Yuan-Ming YehMolecular Medicine Research Center, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist, Taoyuan City, 333, Taiwan, Republic of China.
Hsien-Chi FanDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
An-Chi LinDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Yen-Jung LuACT Genomics, Co. Ltd., 1F., No.280, Xinhu 2nd Rd., Neihu Dist, Taipei City, 114, Taiwan, Republic of China.
Chia-Hsun HsiehDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Kai-Ping ChangDepartment of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Ngan-Ming TsangDepartment of Radiation, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Hung-Ming WangDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China.
Alex Y ChangJohns Hopkins Singapore International Medical Centre, 11 Jalan Tan Tock Seng, Singapore City, 308433, Singapore.
Yu-Sun ChangDepartment of Microbiology and Immunology, Molecular Medicine Research Center, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Lin-Kou, Taoyuan, 333, Taiwan, Republic of China.
Hsin-Pai LiDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No.5, Fuxing St., Guishan Dist, Taoyuan City, 333, Lin-Kou, Taiwan, Republic of China. paili@mail.cgu.edu.tw.
Chang Gung University · TWChang Gung Memorial Hospital · TWGenomics Research Center, Academia Sinica · TW

Funding

Chang Gung Memorial Hospital, Linkou CMRPD3E0071~2, CMRPD1G0471Chang Gung Memorial Hospital, Linkou CMRPG-3C1931~3, -3F0011~2Chang Gung Memorial Hospital, Linkou CMRPG3E1131~2Ministry of Education, Taiwan EMRPD-1G0151, -1H027Ministry of Science and Technology, Taiwan MOST104-2320-B-182-033-MY3Ministry of Science and Technology, Taiwan MOST105-2314-B-182-063-MY2
6 · The paper itself

Abstract

backgroundPatient-derived xenograft (PDX) tumor model has become a new approach in identifying druggable tumor mutations, screening and evaluating personalized cancer drugs based on the mutated targets.

methodsWe established five nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome sequencing (WES) and genomic mutation analyses were performed to search for genetic alterations for new drug targets. Potential drugs were applied in two NPC PDX mice model to assess their anti-cancer activities. RNA sequencing and transcriptomic analysis were performed in one NPC PDX mice to correlate with the efficacy of the anti-cancer drugs.

resultsA relative high incident rate of copy number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in > 90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients' plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with liver metastatic was treated with Palbociclib, had stable disease response and a drop in Epstein Barr virus (EBV) EBV titer.

conclusionsOur integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC.

Indexed as

AdolescentAdultAnimalsCarcinomaCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18DNA Copy Number VariationsExome SequencingFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHerpesvirus 4, HumanHumansMaleMiceCCND1 protein, humanCDKN2A protein, humanCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18palbociclibPiperazinesProtein Kinase InhibitorsPyridinesCDK4/6 inhibitorEBVNasopharyngeal carcinomaPatient derived xenograftRNA sequencingWhole-exome sequencing

Identifiers

PMID30236142
PMCPMC6149192
OpenAlexW2890218349

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LicenceCC BY
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Registered trials

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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.