دورية أكاديمية
Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC
العنوان: | Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC |
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المؤلفون: | Negrao, Marcelo V, Araujo, Haniel A, Lamberti, Giuseppe, Cooper, Alissa J, Akhave, Neal S, Zhou, Teng, Delasos, Lukas, Hicks, J Kevin, Aldea, Mihaela, Minuti, Gabriele, Hines, Jacobi, Aredo, Jacqueline V, Dennis, Michael J, Chakrabarti, Turja, Scott, Susan C, Bironzo, Paolo, Scheffler, Matthias, Christopoulos, Petros, Stenzinger, Albrecht, Riess, Jonathan W, Kim, So Yeon, Goldberg, Sarah B, Li, Mingjia, Wang, Qi, Qing, Yun, Ni, Ying, Do, Minh Truong, Lee, Richard, Ricciuti, Biagio, Alessi, Joao Victor, Wang, Jing, Resuli, Blerina, Landi, Lorenza, Tseng, Shu-Chi, Nishino, Mizuki, Digumarthy, Subba R, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Vaporciyan, Ara A, Blumenschein, George R, Zhang, Jianjun, Owen, Dwight H, Blakely, Collin M, Mountzios, Giannis, Shu, Catherine A, Bestvina, Christine M, Garassino, Marina Chiara, Marrone, Kristen A, Gray, Jhanelle E, Patel, Sandip Pravin, Cummings, Amy L, Wakelee, Heather A, Wolf, Juergen, Scagliotti, Giorgio Vittorio, Cappuzzo, Federico, Barlesi, Fabrice, Patil, Pradnya D, Drusbosky, Leylah, Gibbons, Don L, Meric-Bernstam, Funda, Lee, J Jack, Heymach, John V, Hong, David S, Heist, Rebecca S, Awad, Mark M, Skoulidis, Ferdinandos |
المساهمون: | Negrao, Marcelo V, Araujo, Haniel A, Lamberti, Giuseppe, Cooper, Alissa J, Akhave, Neal S, Zhou, Teng, Delasos, Luka, Hicks, J Kevin, Aldea, Mihaela, Minuti, Gabriele, Hines, Jacobi, Aredo, Jacqueline V, Dennis, Michael J, Chakrabarti, Turja, Scott, Susan C, Bironzo, Paolo, Scheffler, Matthia, Christopoulos, Petro, Stenzinger, Albrecht, Riess, Jonathan W, Kim, So Yeon, Goldberg, Sarah B, Li, Mingjia, Wang, Qi, Qing, Yun, Ni, Ying, Do, Minh Truong, Lee, Richard, Ricciuti, Biagio, Alessi, Joao Victor, Wang, Jing, Resuli, Blerina, Landi, Lorenza, Tseng, Shu-Chi, Nishino, Mizuki, Digumarthy, Subba R, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Vaporciyan, Ara A, Blumenschein, George R, Zhang, Jianjun, Owen, Dwight H, Blakely, Collin M, Mountzios, Gianni, Shu, Catherine A, Bestvina, Christine M, Garassino, Marina Chiara, Marrone, Kristen A, Gray, Jhanelle E, Patel, Sandip Pravin, Cummings, Amy L, Wakelee, Heather A, Wolf, Juergen, Scagliotti, Giorgio Vittorio, Cappuzzo, Federico, Barlesi, Fabrice, Patil, Pradnya D, Drusbosky, Leylah, Gibbons, Don L, Meric-Bernstam, Funda, Lee, J Jack, Heymach, John V, Hong, David S, Heist, Rebecca S, Awad, Mark M, Skoulidis, Ferdinandos |
سنة النشر: | 2023 |
المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
مصطلحات موضوعية: | KRASG12C Inhibitor, Advanced NSCLC |
الوصف: | Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) effi cacy in advanced KRASG12C- mutant NSCLC are poorly defi ned. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identifi ed and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured & SIM;50% of those with early disease progres-sion (progression-free survival & LE; 3 months) with KRASG12Ci. Pathway-level integration of less preva-lent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifi cations, as candidate drivers of inferior outcomes with KRASG12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRASG12Ci effi cacy. Our fi ndings propose a framework for patient stratifi cation and clinical outcome prediction in KRASG12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies.SIGNIFICANCE: In this work, we identify co-occurring genomic alterations in KEAP1, SMARCA4, and CDKN2A as independent determinants of poor clinical outcomes with KRASG12Ci monotherapy in advanced NSCLC, and we propose a framework for patient stratifi cation and treatment personalization based on the comutational status of individual tumors. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/37068173; info:eu-repo/semantics/altIdentifier/wos/WOS:001046642600001; volume:13; issue:7; firstpage:1556; lastpage:1571; numberofpages:16; journal:CANCER DISCOVERY; https://hdl.handle.net/2318/1935630Test; https://aacrjournals.org/cancerdiscovery/article/13/7/1556/727614/Comutations-and-KRASG12C-Inhibitor-Efficacy-inTest |
DOI: | 10.1158/2159-8290.CD-22-1420 |
الإتاحة: | https://doi.org/10.1158/2159-8290.CD-22-1420Test https://hdl.handle.net/2318/1935630Test https://aacrjournals.org/cancerdiscovery/article/13/7/1556/727614/Comutations-and-KRASG12C-Inhibitor-Efficacy-inTest |
حقوق: | info:eu-repo/semantics/closedAccess |
رقم الانضمام: | edsbas.F07788C9 |
قاعدة البيانات: | BASE |
DOI: | 10.1158/2159-8290.CD-22-1420 |
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