PMID- 31186738
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 17
IP  - 6
DP  - 2019 Jun
TI  - Transformation to small cell lung cancer and activation of KRAS during long-term 
      erlotinib maintenance in a patient with non-small cell lung cancer: A case 
      report.
PG  - 5219-5223
LID - 10.3892/ol.2019.10196 [doi]
AB  - Epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer 
      (non-SCLC) benefits from first-line treatment with first generation tyrosine 
      kinase inhibitors (TKIs). However, drug resistance is inevitable through 
      different mechanisms and is dominated by the acquisition of the T790M mutation 
      within EGFR, which occurs in ~50% of cases. The present study reports the case of 
      a patient originally diagnosed with stage IA lung adenocarcinoma, with a 
      recurrent tumor lesion in each side of the lungs following the surgical removal 
      of the primary tumor. Erlotinib treatment of the recurrent tumors eliminated the 
      tumor on the right side of the lung and resulted in the histological 
      transformation of the tumor on the left side to SCLC following 6 years of 
      treatment. Genetic profiling of the SCLC lesions using targeted next-generation 
      sequencing identified different genetic alterations from the primary tumor, 
      characterized by the newly acquired copy number loss of tumor protein p53 and 
      transcriptional coreceptor 1, and the copy number gain of SRY-box 2. Continuation 
      of treatment with chemotherapy and erlotinib demonstrated moderate disease 
      control for ~1 year prior to the outbreak of a new lung lesion. Liquid biopsy 
      profiling of circulating tumor DNA revealed the acquisition of KRAS 
      proto-oncogene, GTPase (KRAS) p.G12C mutation, indicating the occurrence of 
      another resistance mechanism to erlotinib. During erlotinib treatment, the lung 
      adenocarcinoma progressed through two atypical mechanisms, notably from the 
      transformation to SCLC and the acquisition of the KRAS mutation to surpass EGFR 
      inhibition. However, the combinational and interchanging usage of chemotherapy 
      and TKI resulted in persistent and effective disease control.
FAU - Gu, Yangchun
AU  - Gu Y
AD  - Department of Chemotherapy and Radiation Sickness, Peking University 3rd 
      Hospital, Beijing 100191, P.R. China.
FAU - Zhu, Xiang
AU  - Zhu X
AD  - Department of Pathology, Peking University 3rd Hospital, Beijing 100191, P.R. 
      China.
FAU - Cao, Baoshan
AU  - Cao B
AD  - Department of Chemotherapy and Radiation Sickness, Peking University 3rd 
      Hospital, Beijing 100191, P.R. China.
FAU - Wu, Xue
AU  - Wu X
AD  - Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON 
      M5G 1L7, Canada.
FAU - Tong, Xiaoling
AU  - Tong X
AD  - Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON 
      M5G 1L7, Canada.
FAU - Shao, Yang W
AU  - Shao YW
AD  - Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON 
      M5G 1L7, Canada.
AD  - School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, 
      P.R. China.
FAU - Liang, Li
AU  - Liang L
AD  - Department of Chemotherapy and Radiation Sickness, Peking University 3rd 
      Hospital, Beijing 100191, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190328
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC6507320
OTO - NOTNLM
OT  - KRAS mutation
OT  - epidermal growth factor receptor
OT  - erlotinib
OT  - next-generation sequencing
OT  - non-small cell lung cancer
OT  - small cell lung cancer
EDAT- 2019/06/13 06:00
MHDA- 2019/06/13 06:01
PMCR- 2019/03/28
CRDT- 2019/06/13 06:00
PHST- 2018/05/27 00:00 [received]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/06/13 06:00 [entrez]
PHST- 2019/06/13 06:00 [pubmed]
PHST- 2019/06/13 06:01 [medline]
PHST- 2019/03/28 00:00 [pmc-release]
AID - OL-0-0-10196 [pii]
AID - 10.3892/ol.2019.10196 [doi]
PST - ppublish
SO  - Oncol Lett. 2019 Jun;17(6):5219-5223. doi: 10.3892/ol.2019.10196. Epub 2019 Mar 
      28.