Evidence mapPaperPMID 37534247Full record

ArticleFrontiers in oncology2023

PLX4032 resistance of patient-derived melanoma cells: crucial role of oxidative metabolism.

Ombretta Garbarino, Giulia Elda Valenti, Lorenzo Monteleone, Gabriella Pietra, Maria Cristina Mingari, Andrea Benzi, Santina Bruzzone, Silvia Ravera, Riccardo Leardi, Emanuele Farinini and 4 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

8 citing papers in PubMed, 9 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

14 authors at 2 institutions in 1 country.

Ombretta GarbarinoDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Giulia Elda ValentiDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Lorenzo MonteleoneDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Gabriella PietraDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Maria Cristina MingariDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Andrea BenziDepartment of Experimental Medicine, Biochemistry Section, University of Genoa, Genoa, Italy.
Santina BruzzoneIRCCS Ospedale Policlinico San Martino, Genova, Italy.
Silvia RaveraDepartment of Experimental Medicine, Human Anatomy Section, University of Genoa, Genoa, Italy.
Riccardo LeardiDepartment of Pharmacy, University of Genoa, Genoa, Italy.
Emanuele FarininiDepartment of Pharmacy, University of Genoa, Genoa, Italy.
Stefania VernazzaDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Melania GrottoliDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Barbara MarengoDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
Cinzia DomenicottiDepartment of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy.
University of Genoa · ITOspedale Policlinico San Martino · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Malignant melanoma is the most lethal form of skin cancer which shows BRAF mutation in 50% of patients. In this context, the identification of BRAF Methods: The herein reported model has been realized by treating with PLX4032, for six months, patient-derived BRAF-mutated melanoma cells in order to obtain a reliable model of acquired PLX4032 resistance that could be predictive of patient's treatment responses. Metabolic analyses were performed by evaluating glucose consumption, ATP synthesis, oxygen consumption rate, P/O ratio, ATP/AMP ratio, lactate release, lactate dehydrogenase activity, NAD Results: Collectively, our results demonstrate, for the first time in patient-derived melanoma cells, that the rewiring of oxidative phosphorylation and the maintenance of pyruvate dehydrogenase activity and of high glutathione levels contribute to trigger the onset of PLX4032 resistance. Conclusion: Therefore, it is possible to hypothesize that inhibitors of glutathione biosynthesis and/or pyruvate dehydrogenase activity could be used in combination with PLX4032 to overcome drug resistance of BRAF-mutated melanoma patients. However, the identification of new adjuvant targets related to drug-induced metabolic reprogramming could be crucial to counteract the failure of targeted therapy in metastatic melanoma.

Indexed as

BRAFglutathionemelanomaoxidative metabolismPLX4032pyruvate dehydrogenasetargeted therapy resistance

Identifiers

PMID37534247
PMCPMC10391174
OpenAlexW4384695207

What Socratic holds

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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 Socratic graph.