Evidence map›Paper›PMID 21278246›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011

Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.

Gottfried E Konecny, Boris Winterhoff, Teodora Kolarova, Jingwei Qi, Kanthinh Manivong, Judy Dering, Guorong Yang, Meenal Chalukya, He-Jing Wang, Lee Anderson and 11 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% 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

187 citing papers in PubMed, 1 synthesis or guideline pooled it, 297 citations in OpenAlex.

  1. Pooled it
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  3. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2015
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127 more citing papers are in PubMed but not listed here.

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

21 authors at 5 institutions in 1 country.

Gottfried E KonecnyDivision of Hematology-Oncology, Department of Biomathematics and Biostatistics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. gkonecny@mednet.ucla.edu
Boris Winterhoff
Teodora Kolarova
Jingwei Qi
Kanthinh Manivong
Judy Dering
Guorong Yang
Meenal Chalukya
He-Jing Wang
Lee Anderson
Kimberly R Kalli
Richard S Finn
Charles Ginther
Siân Jones
Victor E Velculescu
Darren Riehle
William A Cliby
Sophia Randolph
Maria Koehler
Lynn C Hartmann
Dennis J Slamon
Mayo Clinic · USUniversity of California, Los Angeles · USJohns Hopkins University · USSidney Kimmel Cancer Center · USCancer Genetics (United States) · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

purposePD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer. EXPERIMENTAL

designWe examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and array CGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort of ovarian cancer patients.

resultsConcentration-dependent antiproliferative effects of PD-0332991 were seen in all ovarian cancer cell lines, but varied significantly between individual lines. Rb-proficient cell lines with low p16 expression were most responsive to CDK4/6 inhibition. Copy number variations of CDKN2A, RB, CCNE1, and CCND1 were associated with response to PD-0332991. CDK4/6 inhibition induced G0/G1 cell cycle arrest, blocked Rb phosphorylation in a concentration-and time-dependent manner, and enhanced the effects of chemotherapy. Rb-proficiency with low p16 expression was seen in 97/262 (37%) of ovarian cancer patients and was independently associated with poor progression-free survival (adjusted relative risk 1.49, 95% CI 1.00-2.24, P = 0.052).

conclusionsPD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer.

Indexed as

Gene Expression Regulation, NeoplasticGenes, p16Cell CycleCell Line, TumorCell ProliferationCohort StudiesCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p16Dose-Response Relationship, DrugFemaleGenes, p53HumansImmunohistochemistryOligonucleotide Array Sequence AnalysisOvarian NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p16palbociclibPiperazinesPyridinesRetinoblastoma Protein

Identifiers

PMID21278246
PMCPMC4598646
OpenAlexW2144241792

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.