DARPP-32 and t-DARPP in the development of resistance to anti-HER2 agents. Pre-clinical evidence from the STEP study.

Autor:	Bon G; Department of Research, Cellular Network and Molecular Therapeutic Target Unit, Diagnosis and Innovative Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Krasniqi E; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53, Rome 00144, Italy., Porru M; Department of Research, Diagnosis and Innovative Technologies, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., D'Ambrosio L; Department of Research, Diagnosis and Innovative Technologies, Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Scalera S; SAFU Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy; Department of Biology, PhD Program in Cellular and Molecular Biology, University of Rome 'Tor Vergata', Rome, Italy., Maugeri-Saccà M; Clinical Trial Center, Biostatistics and Bioinformatics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53, Rome 00144, Italy., Di Lisa FS; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Filomeno L; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Arcuri T; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy; Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology A, Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy., Botticelli A; Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology A, Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy., Santini D; Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology A, Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy., Fabbri MA; Medical Oncology Unit, Belcolle Hospital, Viterbo, Italy., D'Auria G; Medical Oncology, Sandro Pertini Hospital, Rome, Italy., Pulito C; Oncogenomic and Epigenetic Unit, IRCCS, Regina Elena National Cancer Institute, Rome, Italy., Blandino G; Oncogenomic and Epigenetic Unit, IRCCS, Regina Elena National Cancer Institute, Rome, Italy., Marchiò C; Department of Medical Sciences, University of Turin, Turin, Italy; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Barba M; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53, Rome 00144, Italy. Electronic address: maddalena.barba@ifo.it., Ciliberto G; Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Vici P; Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Pizzuti L; Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53, Rome 00144, Italy.
Jazyk:	angličtina
Zdroj:	Neoplasia (New York, N.Y.) [Neoplasia] 2023 Nov; Vol. 45, pp. 100937. Date of Electronic Publication: 2023 Sep 26.
DOI:	10.1016/j.neo.2023.100937
Abstrakt:	The therapeutic scenario of Human Epidermal Growth Factor Receptor 2 positive advanced breast cancer (ABC) has been recently enriched by a number of innovative agents, which are reshaping treatment sequence. While randomized trials have documented an advantage in terms of efficacy, for the newly available agents we lack effectiveness and tolerability evidence from the real-world setting. Similarly, the identification of predictive biomarkers might improve clinical decision. We herein describe the outline of a prospective/retrospective study which aims to explore the optimal sequence of treatment in HER2+, pertuzumab pre-treated ABC patients treated in II line with anti-HER2 agents in clinical practice. As part of the pre-clinical tasks envisioned by the STEP study, in vitro cell models of resistance were exploited to investigate molecular features associated with reduced efficacy of HER2 targeting agents at the transcript level. The aggressive behavior of resistant cell populations was measured by growth assessment in mouse models. This approach led to the identification of DARPP-32 and t-DARPP proteins as possible predictive biomarkers of efficacy of anti-HER2 agents. Biomarkers validation and the clinical goals will be reached through patients' inclusion into two independent cohorts, i.e., the prospective and retrospective cohorts, whose setup is currently ongoing. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FSDL: Ipsen and Novartis, outside the submitted work. AB: Pfizer, Roche, Lilly, Novartis, Msd, Seagen, Gilead and Daiichi Sankyo, outside the submitted work. DS: Amgen, Astellas, Astrazeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, outside the submitted work. GDA: Novartis, Amgen, Eli Lilly, outside the submitted work. CM: Bayer, Roche, AstraZeneca and Daiichi-Sankyo, outside the submitted work. P.V.: Pfizer, Novartis, Eisai, Daiichi Sankyo and Eli Lilly, outside of the manuscript under consideration L.P.: Novartis and Pfizer, outside of the manuscript under consideration. No potential conflicts of interest were disclosed for other authors (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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