Multiple Resistance Mechanisms to Tyrosine Kinase Inhibitors in EGFR Mutated Lung Adenocarcinoma: A Case Report Harboring EGFR Mutations, MET Amplification, and Squamous Cell Transformation

被引：2

作者：

Bruno, Rossella ^{[1
]}

Del Re, Marzia ^{[2
]}

Cucchiara, Federico ^{[2
]}

Petrini, Iacopo ^{[3
]}

Ali, Greta ^{[1
]}

Crucitta, Stefania ^{[2
]}

Proietti, Agnese ^{[1
]}

Valleggi, Simona ^{[4
]}

Chella, Antonio ^{[4
]}

Danesi, Romano ^{[2
]}

Fontanini, Gabriella ^{[5
]}

机构：

[1] Univ Hosp Pisa, Unit Pathol Anat, Pisa, Italy

[2] Univ Hosp Pisa, Dept Clin & Expt Med, Unit Clin Pharmacol & Pharmacogenet, Pisa, Italy

[3] Univ Pisa, Gen Pathol, Pisa, Italy

[4] Univ Hosp Pisa, Unit Pneumol, Pisa, Italy

[5] Univ Pisa, Dept Surg Med Mol Pathol & Crit Area, Pisa, Italy

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

关键词：

EGFR; lung adenocarcinoma; case report; multiple resistance mechanisms; MET amplification; squamous cell transformation; CANCER;

D O I：

10.3389/fonc.2021.674604

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Resistance to EGFR tyrosin kinase inhibitors (TKI) inevitably occurs. Here it is reported the case of a young patient affected by lung adenocarcinoma harboring the L858R EGFR sensitive mutation. The patient developed multiple TKI resistance mechanisms: T790M EGFR resistance mutation, detected only on tumor cell-free DNA, squamous cell transformation and MET amplification, both detected on a tumor re-biopsy. The co-occurrence of squamous cell transformation and de novo MET amplification is an extremely rare event, and this case confirms how dynamic and heterogeneous can be the temporal and spatial tumor evolution under treatment pressure.

引用

收藏

页数：5

相关论文

共 8 条

[1] Impact of TP53 Mutations on Outcome in EGFR-Mutated Patients Treated with First-Line Tyrosine Kinase Inhibitors [J].

Canale, Matteo ;

Petracci, Elisabetta ;

Delmonte, Angelo ;

Chiadini, Elisa ;

Dazzi, Claudio ;

Papi, Maximilian ;

Capelli, Laura ;

Casanova, Claudia ;

De Luigi, Nicoletta ;

Mariotti, Marita ;

Gamboni, Alessandro ;

Chiari, Rita ;

Bennati, Chiara ;

Calistri, Daniele ;

Ludovini, Vienna ;

Crino, Lucio ;

Amadori, Dino ;

Ulivi, Paola .

CLINICAL CANCER RESEARCH, 2017, 23 (09) :2195-2202

[2] Genomic landscape of acquired resistance to third-generation EGFR tyrosine kinase inhibitors in EGFR T790M-mutant non-small cell lung cancer [J].

Lee, Jiyun ;

Kim, Hong Sook ;

Lee, Boram ;

Kim, Hee Kyung ;

Sun, Jong-Mu ;

Ahn, Jin Seok ;

Ahn, Myung-Ju ;

Park, Keunchil ;

Lee, Se-Hoon .

CANCER, 2020, 126 (11) :2704-2712

[3] Treatment of advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines [J].

Passiglia, F. ;

Pilotto, S. ;

Facchinetti, F. ;

Bertolaccini, L. ;

Del Re, M. ;

Ferrara, R. ;

Franchina, T. ;

Malapelle, U. ;

Menis, J. ;

Passaro, A. ;

Ramella, S. ;

Rossi, G. ;

Trisolini, R. ;

Novello, S. .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2020, 146

[4] EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression [J].

Peng, Shunli ;

Wang, Rong ;

Zhang, Xiaojuan ;

Ma, Yueyun ;

Zhong, Longhui ;

Li, Ke ;

Nishiyama, Akihiro ;

Arai, Sachiko ;

Yano, Seiji ;

Wang, Wei .

MOLECULAR CANCER, 2019, 18 (01)

[5] Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment [J].

Shi, Puyu ;

Oh, You Take ;

Zhang, Guojing ;

Yao, Weilong ;

Yue, Ping ;

Li, Yikun ;

Kanteti, Rajani ;

Riehm, Jacob ;

Salgia, Ravi ;

Owonikoko, Taofeek K. ;

Ramalingam, Suresh S. ;

Chen, Mingwei ;

Sun, Shi-Yong .

CANCER LETTERS, 2016, 380 (02) :494-504

[6] Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors [J].

Westover, D. ;

Zugazagoitia, J. ;

Cho, B. C. ;

Lovly, C. M. ;

Paz-Ares, L. .

ANNALS OF ONCOLOGY, 2018, 29 :I10-I19

[7] Third-generation epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer [J].

Wright, Natalie M. Andrews ;

Goss, Glenwood D. .

TRANSLATIONAL LUNG CANCER RESEARCH, 2019, 8 :S247-S264

[8] Impact of MET alterations on targeted therapy with EGFR-tyrosine kinase inhibitors for EGFR-mutant lung cancer [J].

Zhang, Zhe ;

Yang, Sen ;

Wang, Qiming .

BIOMARKER RESEARCH, 2019, 7 (01)