PMID- 35806042 OWN - NLM STAT- MEDLINE DCOM- 20220712 LR - 20220716 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 13 DP - 2022 Jun 24 TI - State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan. LID - 10.3390/ijms23137037 [doi] LID - 7037 AB - Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients' characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care. FAU - Luo, Yung-Hung AU - Luo YH AUID- ORCID: 0000-0002-4194-162X AD - Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Liang, Kung-Hao AU - Liang KH AUID- ORCID: 0000-0002-7593-5965 AD - Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Huang, Hsu-Ching AU - Huang HC AD - Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Shen, Chia-I AU - Shen CI AD - Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Chiang, Chi-Lu AU - Chiang CL AUID- ORCID: 0000-0003-1093-0669 AD - Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Wang, Mong-Lien AU - Wang ML AUID- ORCID: 0000-0002-4060-9131 AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Chiou, Shih-Hwa AU - Chiou SH AD - Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Chen, Yuh-Min AU - Chen YM AUID- ORCID: 0000-0003-0585-8463 AD - Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. LA - eng GR - 109-2314-B-075-083-MY3, 109-2628-B-07-023, 110-2314-B-075-078-MY3, 110-2811-B-075-513, 110-2811-B-075-512, and 110-2321-B-075-001/Ministry of Science and Technology/ GR - V108D46-004-MY2-2, V108E-006-43, V109C-123, V109E-007-3, V110C-140, V110C-197, V111C-138, V111E-001-3, VN111-10, V111C-136, V110E-004-1, and V111E-007-1/Taipei Veterans General Hospital/ PT - Journal Article PT - Review DEP - 20220624 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - ErbB Receptors/metabolism MH - Humans MH - *Lung Neoplasms/pathology MH - Mutation MH - *NF-E2-Related Factor 2/genetics MH - Phosphatidylinositol 3-Kinases/genetics MH - Protein Kinase Inhibitors/pharmacology MH - Proto-Oncogene Proteins c-akt/genetics MH - Taiwan/epidemiology PMC - PMC9266727 OTO - NOTNLM OT - NRF2 OT - Taiwan OT - lung cancer OT - precision medicine OT - proteogenomics OT - targeted therapy COIS- C.-I.S. has received support for attending meetings from Merck Sharp & Dohme. The rest of authors declare that there are no conflict of interest. C.-L.C. has received speaking honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. EDAT- 2022/07/10 06:00 MHDA- 2022/07/14 06:00 PMCR- 2022/06/24 CRDT- 2022/07/09 01:11 PHST- 2022/05/10 00:00 [received] PHST- 2022/06/14 00:00 [revised] PHST- 2022/06/22 00:00 [accepted] PHST- 2022/07/09 01:11 [entrez] PHST- 2022/07/10 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/06/24 00:00 [pmc-release] AID - ijms23137037 [pii] AID - ijms-23-07037 [pii] AID - 10.3390/ijms23137037 [doi] PST - epublish SO - Int J Mol Sci. 2022 Jun 24;23(13):7037. doi: 10.3390/ijms23137037.