Academic Journal
Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development
| العنوان: | Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development |
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| المؤلفون: | Vasseur, Damien, Lacroix, Ludovic, Scoazec, Jean Yves, Pata-Merci, Noémie, Bigot, Ludovic, Flórez-Arango, Juan, Facchinetti, Francesco, Nobre, Catline, da Silva, Alice, Braye, Floriane, Nikolaev, Sergey I., Olaussen, Ken André, André, Fabrice, Ponce, Santiago, Soria, Jean Charles, Besse, Benjamin, Loriot, Yohann, Beshiri, Kristi, Hollebecque, Antoine, Gazzah, Anas, Nicotra, Claudio, Ngo-Camus, Maud, Aldea, Mihaela, Blanc-Durand, Felix, Planchard, David, Barlesi, Fabrice, Tselikas, Lambros, Michiels, Stefan, Jules-Clement, Gérôme, Friboulet, Luc |
| المساهمون: | Institut Gustave Roussy (IGR), Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), The work of L. Friboulet is supported by an ERC Consolidator Grant (agreement number 101044047). The work of D. Vasseur is supported by Institut Servier and by Philippe Foundation. |
| المصدر: | ISSN: 1476-4598 ; Molecular Cancer ; https://hal.science/hal-04758719 ; Molecular Cancer, 2024, 23 (1), ⟨10.1186/s12943-024-02134-4⟩. |
| بيانات النشر: | HAL CCSD BioMed Central |
| سنة النشر: | 2024 |
| المجموعة: | Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| مصطلحات موضوعية: | Biopsy, Cancer, Metastatic, PDX, Resistance, Targeted therapy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | International audience ; Understanding the resistance mechanisms of tumor is crucial for advancing cancer therapies. The prospective MATCH-R trial (NCT02517892), led by Gustave Roussy, aimed to characterize resistance mechanisms to cancer treatments through molecular analysis of fresh tumor biopsies. This report presents the genomic data analysis of the MATCH-R study conducted from 2015 to 2022 and focuses on targeted therapies. Methods: The study included resistant metastatic patients (pts) who accepted an image-guided tumor biopsy. After evaluation of tumor content (TC) in frozen tissue biopsies, targeted NGS (10 < TC < 30%) or Whole Exome Sequencing and RNA sequencing (TC > 30%) were performed before and/or after the anticancer therapy. Patient-derived xenografts (PDX) were established by implanting tumor fragments into NOD scid gamma mice and amplified up to five passages. Results: A total of 1,120 biopsies were collected from 857 pts with the most frequent tumor types being lung (38.8%), digestive (16.3%) and prostate (14.1%) cancer. Molecular targetable driver were identified in 30.9% (n = 265/857) of the patients, with EGFR (41.5%), FGFR2/3 (15.5%), ALK (11.7%), BRAF (6.8%), and KRAS (5.7%) being the most common altered genes. Furthermore, 66.0% (n = 175/265) had a biopsy at progression on targeted therapy. Among resistant cases, 41.1% (n = 72/175) had no identified molecular mechanism, 32.0% (n = 56/175) showed on-target resistance, and 25.1% (n = 44/175) exhibited a by-pass resistance mechanism. Molecular profiling of the 44 patients with by-pass resistance identified 51 variants, with KRAS (13.7%), PIK3CA (11.8%), PTEN (11.8%), NF2 (7.8%), AKT1 (5.9%), and NF1 (5.9%) being the most altered genes. Treatment was tailored for 45% of the patients with a resistance mechanism identified leading to an 11 months median extension of clinical benefit. A total of 341 biopsies were implanted in mice, successfully establishing 136 PDX models achieving a 39.9% success rate. PDX models are available for EGFR ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/39363320; PUBMED: 39363320 |
| DOI: | 10.1186/s12943-024-02134-4 |
| الاتاحة: | https://hal.science/hal-04758719 https://hal.science/hal-04758719v1/document https://hal.science/hal-04758719v1/file/s12943-024-02134-4.pdf https://doi.org/10.1186/s12943-024-02134-4 |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.823B4481 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12943-024-02134-4 |
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