Evidence map›Paper›PMID 29713246›Full record

ArticleCancer cell international2018

Autophagy inhibition improves the cytotoxic effects of receptor tyrosine kinase inhibitors.

Sanja Aveic, Marcella Pantile, Pierfrancesco Polo, Viktoryia Sidarovich, Marilena De Mariano, Alessandro Quattrone, Luca Longo, Gian Paolo Tonini

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

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  13. Review
  14. Autophagy: A Player in response to Oxidative Stress and DNA Damage.Oxidative medicine and cellular longevity · 2019
    Article
  15. Molecularly Targeted Therapy for Neuroblastoma.Children (Basel, Switzerland) · 2018
    Review
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 4 institutions in 1 country.

Sanja AveicNeuroblastoma Laboratory, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.ORCID 0000-0002-3886-4360
Marcella PantileNeuroblastoma Laboratory, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.
Pierfrancesco Polo2University of Padua, Padua, Italy.
Viktoryia Sidarovich3Centre for Integrative Biology, University of Trento, Trento, Italy.
Marilena De MarianoUOC Bioterapie, Ospedale Policlinico San Martino, Genoa, Italy.
Alessandro Quattrone3Centre for Integrative Biology, University of Trento, Trento, Italy.
Luca LongoUOC Bioterapie, Ospedale Policlinico San Martino, Genoa, Italy.
Gian Paolo ToniniNeuroblastoma Laboratory, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.
Città della Speranza Foundation · ITOspedale Policlinico San Martino · ITUniversity of Trento · ITUniversity of Padua · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA growing field of evidence suggests the involvement of oncogenic receptor tyrosine kinases (RTKs) in cell transformation. Deregulated activity of RTKs in tumors can determine disease progression and therapeutic responses in several types of cancer, including neuroblastoma (NB). Therefore, RTKs targeting is a worthwhile challenge for the oncologists. Nevertheless, acquired resistance to RTK inhibitors (RTKi) remains a serious problem. Autophagy activation is among the possible obstacles for good efficacy of the therapy with RTKi.

methodsUnder different treatment conditions we measured autophagic flux using immunoblot and immunofluorescence assays. Death induction was validated by trypan blue exclusion assay and FACS analysis (calcein-AM/propidium iodide). The NB cell lines SH-SY5Y and Kelly were used for the in vitro study.

resultsIn order to define whether autophagy might be a limiting factor for the efficacy of RTKi in NB cells, we firstly checked its activation following the treatment with several RTKi. Next, we investigated the possibility to increase their therapeutic efficiency by combining RTKi with autophagy blocking agents in vitro. We exploited the effectiveness of three RTKi either alone or in combination with autophagy inhibitors (Chloroquine-CQ and Spautin-1). We demonstrated that autophagy induction was drug-dependent, and that its inhibition increased the anti-tumor activity of a single RTKi unevenly. We observed that the combined use of blocking agents which impair late autophagy events, such as CQ, and RTKi can be more effective with respect to the use of RTKi alone.

conclusionsIn the present report, we assessed the conditions under which autophagy is activated during the use of different RTKi currently in the pre-clinical evaluation for NB. We summarized the achievements of combined RTK/autophagy inhibitors treatment as a promising approach to enhance the efficacy of RTKi in impairing tumor cells viability.

Indexed as

AutophagyDrug combinationNeuroblastomaRTK inhibitors

Identifiers

PMID29713246
PMCPMC5916832
OpenAlexW2799323203

What OpenQuestion holds

Textmetadata
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.