Evidence map›Paper›PMID 28886696›Full record

ArticleBMC cancer2017

Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors.

Charles-André Philip, Ido Laskov, Marie-Claude Beauchamp, Maud Marques, Oreekha Amin, Joanna Bitharas, Roy Kessous, Liron Kogan, Tahira Baloch, Walter H Gotlieb and 1 more

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

Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
12.7field-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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

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2 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

11 authors at 3 institutions in 2 countries.

Charles-André PhilipSegal Cancer Center, Lady Davis Institute of Medical Research, McGill University, 3755 Cote Ste. Catherine Road, Montreal, QC, H3T 1E2, Canada.
Ido LaskovDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Marie-Claude BeauchampDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Maud MarquesSegal Cancer Center, Lady Davis Institute of Medical Research, McGill University, 3755 Cote Ste. Catherine Road, Montreal, QC, H3T 1E2, Canada.
Oreekha AminSegal Cancer Center, Lady Davis Institute of Medical Research, McGill University, 3755 Cote Ste. Catherine Road, Montreal, QC, H3T 1E2, Canada.
Joanna BitharasSegal Cancer Center, Lady Davis Institute of Medical Research, McGill University, 3755 Cote Ste. Catherine Road, Montreal, QC, H3T 1E2, Canada.
Roy KessousDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Liron KoganDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Tahira BalochSegal Cancer Center, Lady Davis Institute of Medical Research, McGill University, 3755 Cote Ste. Catherine Road, Montreal, QC, H3T 1E2, Canada.
Walter H GotliebDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Amber YasmeenDivision of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada. amber.yasmeen@mail.mcgill.ca.ORCID http://orcid.org/0000-0002-7445-3032
Jewish General Hospital · CAMcGill University · CATel Aviv University · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70-80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair.

methodsUsing endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay. The 50% Inhibitory concentration (IC50) of PI3K and PARP inhibitors in these cells was assessed, and western blotting was performed to determine the expression of proteins involved in the PI3K/mTOR pathway. Moreover, we explored the interaction between RAD51 and PI3K/mTOR by immunofluorescence. Next, the combination effect of PI3K and PARP inhibitors on cell proliferation was evaluated by a clonogenic assay.

resultsCells with mutated PTEN showed over-activation of the PI3K/mTOR pathway. These cells were more sensitive to PARP inhibition compared to PTEN wild-type cells. In addition, PI3K inhibitor treatment reduced RAD51 foci formation in PTEN mutated cells, and sensitized these cells to PARP inhibitor.

conclusionTargeting both PARP and PI3K might lead to improved personalized therapeutic approaches in endometrial cancer patients with PTEN mutations. Understanding the complex interaction of PTEN mutations with DNA repair in endometrial cancer will help to better select patients that are likely to respond to some of the new and costly targeted therapies.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCell ProliferationDNA RepairDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansMutationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPTEN PhosphohydrolaseMTOR protein, humanolaparibPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPTEN PhosphohydrolasePTEN protein, humanRad51 RecombinasetalazoparibTOR Serine-Threonine KinasesDNA repair pathwayEndometrial cancerPARP inhibitorPI3K/mTOR pathwayPTENRAD51

Identifiers

PMID28886696
PMCPMC5591502
OpenAlexW2750919339

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.