Evidence map›Paper›PMID 25195596›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014

Lentiviral vector-based insertional mutagenesis identifies genes involved in the resistance to targeted anticancer therapies.

Marco Ranzani, Stefano Annunziato, Andrea Calabria, Stefano Brasca, Fabrizio Benedicenti, Pierangela Gallina, Luigi Naldini, Eugenio Montini

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Production of Lentiviral Vectors Using Suspension Cells Grown in Serum-free Media.Molecular therapy. Methods & clinical development · 2020
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
  10. Article
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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

8 authors at 2 institutions in 3 countries.

Marco RanzaniSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Current address: Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Cambridge, UK.
Stefano AnnunziatoSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Current address: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Stefano BrascaSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Fabrizio BenedicentiSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Pierangela GallinaSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Luigi NaldiniSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy.
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy. Electronic address: montini.eugenio@hsr.it.
The San Raffaele Telethon Institute for Gene Therapy · ITOncode Institute · NL

Funding

Telethon TGT11D01
6 · The paper itself

Abstract

The high transduction efficiency of lentiviral vectors in a wide variety of cells makes them an ideal tool for forward genetics screenings addressing issues of cancer research. Although molecular targeted therapies have provided significant advances in tumor treatment, relapses often occur by the expansion of tumor cell clones carrying mutations that confer resistance. Identification of the culprits of anticancer drug resistance is fundamental for the achievement of long-term response. Here, we developed a new lentiviral vector-based insertional mutagenesis screening to identify genes that confer resistance to clinically relevant targeted anticancer therapies. By applying this genome-wide approach to cell lines representing two subtypes of HER2(+) breast cancer, we identified 62 candidate lapatinib resistance genes. We validated the top ranking genes, i.e., PIK3CA and PIK3CB, by showing that their forced expression confers resistance to lapatinib in vitro and found that their mutation/overexpression is associated to poor prognosis in human breast tumors. Then, we successfully applied this approach to the identification of erlotinib resistance genes in pancreatic cancer, thus showing the intrinsic versatility of the approach. The acquired knowledge can help identifying combinations of targeted drugs to overcome the occurrence of resistance, thus opening new horizons for more effective treatment of tumors.

Indexed as

Drug Resistance, NeoplasmBreast NeoplasmsCell Line, TumorClass I Phosphatidylinositol 3-KinasesErlotinib HydrochlorideFemaleGenetic VectorsHumansLapatinibLentivirusMolecular Targeted TherapyMutagenesis, InsertionalPancreatic NeoplasmsPhosphatidylinositol 3-KinasesPrognosisProtein Kinase InhibitorsClass I Phosphatidylinositol 3-KinasesErlotinib HydrochlorideLapatinibPhosphatidylinositol 3-KinasesPIK3CA protein, humanPIK3CB protein, humanProtein Kinase InhibitorsQuinazolines

Identifiers

PMID25195596
PMCPMC4429698
OpenAlexW2037200017

What OpenQuestion holds

Textmetadata
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.