TK-1, TP, Ang-2, and Tie-2 mRNA expression in plasma-derived microvesicles of chemo-refractory metastatic colorectal cancer patients.


Journal

Tumori
ISSN: 2038-2529
Titre abrégé: Tumori
Pays: United States
ID NLM: 0111356

Informations de publication

Date de publication:
Oct 2023
Historique:
medline: 29 9 2023
pubmed: 8 1 2023
entrez: 7 1 2023
Statut: ppublish

Résumé

Trifluridine/tipiracil and regorafenib are indicated for metastatic colorectal cancer (mCRC) patients' refractory to standard chemotherapy. No prognostic or predictive biomarkers are available for these agents. We assessed messenger ribonucleic acid (mRNA) expression of four biomarkers implicated in the mechanism of action of trifluridine/tipiracil (TK-1 and TP) and regorafenib (Ang-2 and Tie-2) in baseline plasma-derived microvesicles of chemo-refractory mCRC patients treated with these agents (trifluridine/tipiracil cohort and regorafenib cohort), to explore their prognostic and predictive role. Baseline characteristics of the two cohorts were not different. Ang-2 mRNA was not detectable. Only TK-1 expression measured as a continuous variable was associated with progression-free survival (HR=1.09, 95%CI: 0.99-1.21; p=0.07) and overall survival (HR=1.11, 95%CI: 1.00-1.22; p=0.04), confirmed at multivariate analysis for progression-free survival (p=0.02) with a positive trend for overall survival (p=0.08). Baseline mRNA levels of TK-1, TP and Tie-2 were not predictive of trifluridine/tipiracil and regorafenib benefit. Baseline mRNA levels of TK-1, TP and Tie-2 on plasma-derived microvesicles were not predictive of trifluridine/tipiracil and regorafenib benefit. Future studies should analyze the early modulation of these biomarkers to assess their potential predictive role.

Sections du résumé

BACKGROUND UNASSIGNED
Trifluridine/tipiracil and regorafenib are indicated for metastatic colorectal cancer (mCRC) patients' refractory to standard chemotherapy. No prognostic or predictive biomarkers are available for these agents.
METHODS UNASSIGNED
We assessed messenger ribonucleic acid (mRNA) expression of four biomarkers implicated in the mechanism of action of trifluridine/tipiracil (TK-1 and TP) and regorafenib (Ang-2 and Tie-2) in baseline plasma-derived microvesicles of chemo-refractory mCRC patients treated with these agents (trifluridine/tipiracil cohort and regorafenib cohort), to explore their prognostic and predictive role.
RESULTS UNASSIGNED
Baseline characteristics of the two cohorts were not different. Ang-2 mRNA was not detectable. Only TK-1 expression measured as a continuous variable was associated with progression-free survival (HR=1.09, 95%CI: 0.99-1.21; p=0.07) and overall survival (HR=1.11, 95%CI: 1.00-1.22; p=0.04), confirmed at multivariate analysis for progression-free survival (p=0.02) with a positive trend for overall survival (p=0.08). Baseline mRNA levels of TK-1, TP and Tie-2 were not predictive of trifluridine/tipiracil and regorafenib benefit.
CONCLUSION UNASSIGNED
Baseline mRNA levels of TK-1, TP and Tie-2 on plasma-derived microvesicles were not predictive of trifluridine/tipiracil and regorafenib benefit. Future studies should analyze the early modulation of these biomarkers to assess their potential predictive role.

Identifiants

pubmed: 36609197
doi: 10.1177/03008916221147944
doi:

Substances chimiques

regorafenib 24T2A1DOYB
Uracil 56HH86ZVCT
Trifluridine RMW9V5RW38
Drug Combinations 0
Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

481-489

Auteurs

Beatrice Borelli (B)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Stefania Crucitta (S)

Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Alessandra Boccaccino (A)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Maria Antista (M)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Carlotta Antoniotti (C)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Federica Marmorino (F)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Daniele Rossini (D)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Veronica Conca (V)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Marco Maria Germani (MM)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Leonardo Provenzano (L)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Andrea Spagnoletti (A)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Alberto Giovanni Leone (AG)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Federico Cucchiara (F)

Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Filippo Pietrantonio (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.

Marzia Del Re (M)

Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Romano Danesi (R)

Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Gianluca Masi (G)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Chiara Cremolini (C)

Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Roberto Moretto (R)

Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

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