New Preclinical and Clinical Approaches to Mesothelioma

Официальное название

New Preclinical and Clinical Approaches to Mesothelioma, an Archetypal Inflammatory Tumor

Обзор

This study protocol involves the coordination between UO1 (IRCCS San Raffaele Hospital) and UO2 (Istituto Nazionale Tumori di Napoli - IRCCS G. Pascale) to explore the role of HMGB1 and CXCR4 in cancer treatment and metastasis. UO1 focuses on the role of HMGB1 in inflammation, mesothelioma progression, and tissue repair, as well as developing, in future, possible HMGB1 inhibitors for cancer therapy. UO2 specializes in CXCR4's role in cancer, developing CXCR4 antagonists, and tracking CXCR4-dependent metastasis. The hypothesis is that targeting HMGB1 and CXCR4 pathways will inhibit tumor progression and metastasis, enhancing anti-tumor immunity and improving therapeutic outcomes in cancer.

Подробное описание

This is a multicentric cross-sectional observational study with an additional blood volume collected during blood sampling performed for normal clinical practice. The enrollment will take

Первичные конечные точки

• To set up spheroids models to study and serve as a platform [Срок оценки: 0/baseline]
• To set up spheroids models and serve as a platform [Срок оценки: 0/baseline]
• To set up organoid models [Срок оценки: 0/baseline]
• Test inhibitors on spheroids and organoids and assess the response of individual patients to therapy [Срок оценки: 0/baseline]

Вторичные конечные точки (3)

• To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk [Срок оценки: 0/baseline]
• To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk [Срок оценки: 0/baseline]
• To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk [Срок оценки: In vivo experiment 3 weeks.]

Критерии участия

Критерии включения

• Patients with Mesothelioma:

Clinical suspicion or histologically confirmed diagnosis of pleural mesothelioma.

• Candidates for surgical intervention.
• Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well as breastfeeding women.
• Capacity to comprehend the study nature and provide autonomously informed consent.

Control Group patients:

• Absence of pleural mesothelioma but presence of other histologically confirmed diseases (neoplastic, inflammatory, or infectious).
• Candidates for surgical intervention.
• Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well breastfeeding women.
• Ability to understand the study nature and provide autonomously informed consent.

If the patient's diagnosis, whether provisional or definitive, does not confirm the clinical suspicion, they will not undergo further evaluation in the study.

Критерии исключения

• Lack of biopsy material.
• pregnancy.
• Unwillingness to sign the Informed Consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 2 центра

• Istituto Nazionale Tumori IRCCS Fondazione G.Pascale — Naples
• IRCCS San Raffaele — Milan

Публикации

• Shimizu Y, Dobashi K, Imai H, Sunaga N, Ono A, Sano T, Hikino T, Shimizu K, Tanaka S, Ishizuka T, Utsugi M, Mori M. CXCR4+FOXP3+CD25+ lymphocytes accumulate in CXCL12-expressing malignant pleural mesothelioma. Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):43-51. doi: 10.1177/039463200902200106. PMID 19309551
• Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P, Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev. 2017 Nov;280(1):74-82. doi: 10.1111/imr.12601. PMID 29027228
• Santagata S, Napolitano M, D'Alterio C, Desicato S, Maro SD, Marinelli L, Fragale A, Buoncervello M, Persico F, Gabriele L, Novellino E, Longo N, Pignata S, Perdona S, Scala S. Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer. Oncotarget. 2017 Aug 19;8(44):77110-77120. doi: 10.18632/oncotarget.20363. eCollection 2017 Sep 29. PMID 29100374
• Li B, Zeng Y, Reeves PM, Ran C, Liu Q, Qu X, Liang Y, Liu Z, Yuan J, Leblanc PR, Ye Z, Sluder AE, Gelfand JA, Brauns TA, Chen H, Poznansky MC. AMD3100 Augments the Efficacy of Mesothelin-Targeted, Immune-Activating VIC-008 in Mesothelioma by Modulating Intratumoral Immunosuppression. Cancer Immunol Res. 2018 May;6(5):539-551. doi: 10.1158/2326-6066.CIR-17-0530. Epub 2018 Mar 6. PMID 29511032
• Kinoshita Y, Hamasaki M, Yoshimura M, Matsumoto S, Iwasaki A, Nabeshima K. Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma. Mod Pathol. 2020 Feb;33(2):235-244. doi: 10.1038/s41379-019-0309-6. Epub 2019 Jun 23. PMID 31231129
• D'Alterio C, Buoncervello M, Ierano C, Napolitano M, Portella L, Rea G, Barbieri A, Luciano A, Scognamiglio G, Tatangelo F, Anniciello AM, Monaco M, Cavalcanti E, Maiolino P, Romagnoli G, Arra C, Botti G, Gabriele L, Scala S. Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the tumor microenvironment and inhibiting neoplastic PD-1. J Exp Clin Cancer Res. 2019 Oct 28;38(1):432. doi: 10.1186 PMID 31661001
• Zhang M, Luo JL, Sun Q, Harber J, Dawson AG, Nakas A, Busacca S, Sharkey AJ, Waller D, Sheaff MT, Richards C, Wells-Jordan P, Gaba A, Poile C, Baitei EY, Bzura A, Dzialo J, Jama M, Le Quesne J, Bajaj A, Martinson L, Shaw JA, Pritchard C, Kamata T, Kuse N, Brannan L, De Philip Zhang P, Yang H, Griffiths G, Wilson G, Swanton C, Dudbridge F, Hollox EJ, Fennell DA. Clonal architecture in mesothelioma PMID 33741915
• Bertolini G, Cancila V, Milione M, Lo Russo G, Fortunato O, Zaffaroni N, Tortoreto M, Centonze G, Chiodoni C, Facchinetti F, Pollaci G, Taie G, Giovinazzo F, Moro M, Camisaschi C, De Toma A, D'Alterio C, Pastorino U, Tripodo C, Scala S, Sozzi G, Roz L. A novel CXCR4 antagonist counteracts paradoxical generation of cisplatin-induced pro-metastatic niches in lung cancer. Mol Ther. 2021 Oct 6;29(10): PMID 34023505

Идентификаторы

NCT: NCT06536179 · PNRR-TR1-2023-12377199

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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