Evidence map›Paper›PMID 32055239›Full record

ArticleClinical proteomics2020

Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition.

Mathilde Couëtoux du Tertre, Maud Marques, Suzan McNamara, Karen Gambaro, Cyrla Hoffert, Lise Tremblay, Nicole Bouchard, Razvan Diaconescu, Normand Blais, Christian Couture and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical proteomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

25 authors.

Mathilde Couëtoux du Tertre *Segal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Maud Marques *Segal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Suzan McNamaraSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Karen GambaroSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Cyrla HoffertSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Lise Tremblay3Institut universitaire de cardiologie et pneumologie de Québec, Université de Laval, Québec, QC Canada.
Nicole Bouchard4Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC Canada.
Razvan Diaconescu5Hopital Sacré-Cœur Montréal, Montréal, QC Canada.
Normand Blais6Centre hospitalier universitaire de Montréal, Montréal, QC Canada.
Christian Couture3Institut universitaire de cardiologie et pneumologie de Québec, Université de Laval, Québec, QC Canada.
Vincent PelsserSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Hangjun WangSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Laura McIntosh7Caprion, Montreal, QC Canada.
Valérie Hindie7Caprion, Montreal, QC Canada.
Stephane Parent7Caprion, Montreal, QC Canada.
Laetitia Cortes7Caprion, Montreal, QC Canada.
Yannick-André Breton7Caprion, Montreal, QC Canada.
Gwenael Pottiez7Caprion, Montreal, QC Canada.
Pascal Croteau7Caprion, Montreal, QC Canada.
Valerie HigenellExactis Innovation, Montréal, QC Canada.
Luisa IzziExactis Innovation, Montréal, QC Canada.
Alan SpatzSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Victor CohenSegal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Gerald Batist *Segal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.
Jason Agulnik *Segal Cancer Centre, Jewish General Hospital, McGill University, Jewish General Hospital, 3755, Chemin Cote Ste-Catherine, Montreal, QC H3T1E2 Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib.

methodsTwenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association.

resultsPatients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 < PFS < 24 months (n = 10)] and poor responders [PFS ≤ 3 months (n = 5)]. Several proteins were identified as differentially expressed between long-term responders and poor responders, including DPP4, KIT and LUM. Next, using machine learning algorithms, we evaluated the classification potential of 40 proteins. Finally, by integrating the different analytic methods, we selected 22 proteins as potential candidates for a blood-based prognostic signature of response to crizotinib in NSCLC patients harboring ALK fusion.

conclusionIn conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC. Expanding the utility of prognostic biomarkers of response duration could influence choice of therapy, therapeutic sequencing, and potentially the need for alternative or combination therapy.

Indexed as

CrizotinibLiquid biopsyNSCLCPrediction of responseProtein signature

Identifiers

PMID32055239
PMCPMC7006423

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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.