Evidence map›Paper›PMID 37326340›Full record

ArticleCancer biology & therapy2023

Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer.

Cha Len Lee, Mattia Cremona, Angela Farrelly, Julie A Workman, Sean Kennedy, Razia Aslam, Aoife Carr, Stephen Madden, Brian O'Neill, Bryan T Hennessy and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancer biology & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

16 citing papers in PubMed, 20 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

11 authors at 2 institutions in 1 country.

Cha Len LeeMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Mattia CremonaMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Angela FarrellyMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Julie A WorkmanMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Sean KennedyMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Razia AslamMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Aoife CarrMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Stephen MaddenData Science Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
Brian O'NeillDepartment of Radiation Oncology, St. Luke's Radiation Oncology Centre, Beaumont Hospital, Dublin 9, Ireland.
Bryan T HennessyMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Sinead ToomeyMedical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.ORCID 0000-0002-1365-8173
Royal College of Surgeons in Ireland · IEBeaumont Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStudies have demonstrated the efficacy of Palbociclib (CDK 4/6 inhibitor), Gedatolisib (PI3K/mTOR dual inhibitor) and PD0325901 (MEK1/2 inhibitor) in colorectal cancer (CRC), however single agent therapeutics are often limited by the development of resistance.

methodsWe compared the anti-proliferative effects of the combination of Gedatolisib and Palbociclib and Gedatolisib and PD0325901 in five CRC cell lines with varying mutational background and tested their combinations on total and phosphoprotein levels of signaling pathway proteins.

resultsThe combination of Palbociclib and Gedatolisib was superior to the combination of Palbociclib and PD0325901. The combination of Palbociclib and Gedatolisib had synergistic anti-proliferative effects in all cell lines tested [CI range: 0.11-0.69] and resulted in the suppression of S6rp (S240/244), without AKT reactivation. The combination of Palbociclib and Gedatolisib increased BAX and Bcl-2 levels in

conclusionThis study shows that the combination of Palbociclib and Gedatolisib has synergistic anti-proliferative effects in both wild-type and mutated CRC cell lines. Separately, the phosphorylation of S6rp may be a promising biomarker of responsiveness to this combination.

Indexed as

Colorectal NeoplasmsPhosphatidylinositol 3-KinasesBenzamidesCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4DiphenylamineHumansMitogen-Activated Protein Kinase KinasesPhosphoinositide-3 Kinase InhibitorsPiperazinesProtein Kinase InhibitorsPyridinesBenzamidesCDK4 protein, humanCyclin-Dependent Kinase 4DiphenylaminemirdametinibMitogen-Activated Protein Kinase KinasespalbociclibPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPiperazinesProtein Kinase InhibitorsPyridinesColorectal cancerdrug combinationsGedatolisibpalbociclibS6rp (S240/244)

Identifiers

PMID37326340
PMCPMC10281467
OpenAlexW4380870155

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.