PMID- 38499265
OWN - NLM
STAT- MEDLINE
DCOM- 20240409
LR  - 20240409
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 588
DP  - 2024 Apr 28
TI  - Patient-derived tumoroid models of pulmonary large-cell neuroendocrine carcinoma: 
      a promising tool for personalized medicine and developing novel therapeutic 
      strategies.
PG  - 216816
LID - S0304-3835(24)00209-X [pii]
LID - 10.1016/j.canlet.2024.216816 [doi]
AB  - Pulmonary large-cell neuroendocrine carcinoma (LCNEC), a disease with poor 
      prognosis, is classified as pulmonary high-grade neuroendocrine carcinoma, along 
      with small-cell lung cancer. However, given its infrequent occurrence, only a 
      limited number of preclinical models have been established. Here, we established 
      three LCNEC tumoroids for long-term culture. Whole-exome sequencing revealed that 
      these tumoroids inherited genetic mutations from their parental tumors; two were 
      classified as small-cell carcinoma (S-LCNEC) and one as non-small cell carcinoma 
      (N-LCNEC). Xenografts from these tumoroids in immunodeficient mice mimicked the 
      pathology of the parent LCNEC, and one reproduced the mixed-tissue types of 
      combined LCNEC with a component of adenocarcinoma. Drug sensitivity tests using 
      these LCNEC tumoroids enabled the evaluation of therapeutic agent efficacy. Based 
      on translational research, we found that a CDK4/6 inhibitor might be effective 
      for N-LCNEC and that Aurora A kinase inhibitors might be suitable for S-LCNEC or 
      LCNEC with MYC amplification. These results highlight the value of preclinical 
      tumoroid models in understanding the pathogenesis of rare cancers and developing 
      treatments. LCNEC showed a high success rate in tumoroid establishment, 
      indicating its potential application in personalized medicine.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Yokota, Etsuko
AU  - Yokota E
AD  - Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
FAU - Iwai, Miki
AU  - Iwai M
AD  - General Medical Center Research Unit, Kawasaki Medical School, Okayama, Japan.
FAU - Yukawa, Takuro
AU  - Yukawa T
AD  - Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
FAU - Naomoto, Yoshio
AU  - Naomoto Y
AD  - Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
FAU - Haisa, Minoru
AU  - Haisa M
AD  - Kawasaki Medical School General Medical Center, Okayama, Japan; Department of 
      Medical Care Work, Kawasaki College of Health Professions, Okayama, Japan; 
      Kawasaki Geriatric Medical Center, Okayama, Japan.
FAU - Monobe, Yasumasa
AU  - Monobe Y
AD  - Okayama Medical Laboratories CO., Ltd, Kurashiki, Japan.
FAU - Takigawa, Nagio
AU  - Takigawa N
AD  - General Medical Center Research Unit, Kawasaki Medical School, Okayama, Japan; 
      Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, 
      Japan.
FAU - Fukazawa, Takuya
AU  - Fukazawa T
AD  - Department of General Surgery, Kawasaki Medical School, Okayama, Japan; General 
      Medical Center Research Unit, Kawasaki Medical School, Okayama, Japan. Electronic 
      address: fukazawat@med.kawasaki-m.ac.jp.
FAU - Yamatsuji, Tomoki
AU  - Yamatsuji T
AD  - Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240316
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Precision Medicine
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - *Carcinoma, Neuroendocrine/drug therapy/genetics/pathology
MH  - *Carcinoma, Small Cell/pathology
MH  - *Small Cell Lung Carcinoma/genetics
MH  - *Carcinoma, Large Cell/drug therapy/genetics/pathology
OTO - NOTNLM
OT  - Non-small cell lung cancer
OT  - Personalized medicine
OT  - Pulmonary large-cell neuroendocrine carcinoma
OT  - Small-cell lung cancer
OT  - Tumoroid
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests. T. Yamatsuji reports grants from MSD, Chugai Pharmaceutical, Japan; 
      Takeda Pharmaceutical, Japan; Daiichi-Sankyo, Japan; Kaken Pharmaceutical, Japan; 
      Astellas Pharma, Japan; Eli Lilly Japan, Japan; Shionogi, Japan; Taiho 
      Pharmaceutical, Japan; Bayer Yakuhin, Japan; and Otsuka Pharmaceutical Co., Ltd. 
      Japan and personal fees from Yakult Honsha, Japan outside the submitted work. N. 
      Takigawa reports grants and personal fees from Eli Lilly Japan, Japan; 
      AstraZeneca, United Kingdom; Daiichi-Sankyo, Japan; Chugai Pharmaceutical, Japan; 
      Taiho Pharmaceutical, Japan; Pfizer Inc., United States; Boehringer-Ingelheim 
      Japan, Japan and Ono Pharmaceutical, Japan; grants from Kyowa Hakko Kirin, Japan; 
      Nippon Kayaku, Japan and Takeda Pharmaceutical, Japan and personal fees from MSD 
      and Bristol-Myers Squibb Company, United States outside the submitted work. No 
      disclosures have been reported by the other authors.
EDAT- 2024/03/19 00:42
MHDA- 2024/04/09 06:45
CRDT- 2024/03/18 20:27
PHST- 2023/11/19 00:00 [received]
PHST- 2024/03/04 00:00 [revised]
PHST- 2024/03/12 00:00 [accepted]
PHST- 2024/04/09 06:45 [medline]
PHST- 2024/03/19 00:42 [pubmed]
PHST- 2024/03/18 20:27 [entrez]
AID - S0304-3835(24)00209-X [pii]
AID - 10.1016/j.canlet.2024.216816 [doi]
PST - ppublish
SO  - Cancer Lett. 2024 Apr 28;588:216816. doi: 10.1016/j.canlet.2024.216816. Epub 2024 
      Mar 16.