Lung cancer is the leading cause of cancer death in men and women worldwide. Identification of activating mutations of the epidermal growth factor receptor (EGFR) is one of the most intriguing recent discoveries in the field of lung cancer research.¹ x 1 Paez, JG, Janne, PA, Lee, JC et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497–1500 Crossref | PubMed | Scopus (7036) | Google Scholar See all References ^{, 2} x 2 Lynch, TJ, Bell, DW, Sordella, R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004; 350: 2129–2139 Crossref | PubMed | Scopus (8278) | Google Scholar See all References EGFR mutations are present in one subtype of lung adenocarcinoma, and tumors with this mutation have been shown to be highly sensitive to gefitinib (Iressa). The subtype is prevalent in women, and in patients of Japanese and other Asian ethnicity, especially in nonsmokers.¹ x 1 Paez, JG, Janne, PA, Lee, JC et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497–1500 Crossref | PubMed | Scopus (7036) | Google Scholar See all References ^{, 3} x 3 Pao, W, Miller, V, Zakowski, M et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004; 101: 13306–13311 Crossref | PubMed | Scopus (3316) | Google Scholar See all References ^{, 4} x 4 Shigematsu, H, Lin, L, Takahashi, T et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005; 97: 339–346 Crossref | PubMed | Scopus (1688) | Google Scholar See all References With the move to personalized cancer therapy, we need to understand oncologic biology at the molecular level in individual lesions to be able to treat cancers with specific molecular-targeting strategies.

A subset of lung cancers harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene, EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene), which encodes an activated tyrosine kinase. We have earlier examined the presence of EML4-ALK by multiplex reverse transcription-polymerase chain reaction in 363 specimens of lung cancer, identifying 11 adenocarcinoma cases featuring the fusion gene. In this study, we clinicopathologically examined the characteristics of the EML4-ALK-positive cases, including the mutation status of EGFR, KRAS, and TP53, and whether they were of thyroid transcription factor-1 (TTF-1) cell lineage or not. Of 11 patients, 4 (36%) with EML4-ALK-positive lung adenocarcinomas who were below 50 years of age were affected by these diseases, as compared with 12 of 242 patients (5.0%) with EML4-ALK-negative lung adenocarcinomas (P=0.00038). EML4-ALK-positive lung adenocarcinomas were characterized by less-differentiated grade (P=0.0082) and acinar-predominant structure (P<0.0001) in histology. Furthermore, the presence of EML4-ALK appears to be mutually exclusive for EGFR and KRAS mutations (P=0.00018), whereas coexisting with TP53 mutations at a low frequency (1/11=9.1%), and correlating with non- or light smoking (P=0.040), in line with the TTF-1 immunoreactivity. Thus, EML4-ALK-positive tumors may form a distinct entity among lung adenocarcinomas, characterized by young onset, acinar histology, no or rare mutations in EGFR, KRAS, and TP53, and a TTF-1 cell lineage, all in agreement with the prevalence in non- or light smokers.

Lung cancer is the leading cause of cancer death in men and women worldwide. The lack of specific and sensitive tools for early diagnosis as well as still-inadequate targeted therapies contribute to poor outcomes. MicroRNAs are small non-coding RNAs, which regulate gene expression post-transcriptionally by translational repression or degradation of target mRNAs. A growing body of evidence suggests various roles of microRNAs including development and progression of lung cancer. In lung cancer, several studies have showed that certain microRNA profiles classified lung cancer subtypes, and that specific microRNA expression signatures distinguished between better-prognosis and worse-prognosis lung cancers. Furthermore, microRNAs circulate in body fluids, and therefore may serve as promising biomarkers for early diagnosis of lung cancer as well as for predicting prognosis of patients. In the present review, we briefly summarize microRNAs in the development and progression of lung cancer, focusing on possible applications of microRNAs as novel biomarkers and tools for treatment.

Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes

Small‐cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. To identify accurate predictive biomarkers and effective therapeutic modalities, we focus on a long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR), and investigated its expression, cellular functions, and clinical relevance in SCLC. In this study, HOTAIR expression was assessed in 35 surgical SCLC samples and 10 SCLC cell lines. The efficacy of knockdown of HOTAIR by siRNA transfection was evaluated in SBC‐3 cells in vitro, and the gene expression was analyzed using microarray. HOTAIR was expressed highly in pure, rather than combined, SCLC (P = 0.012), that the subgroup with high expression had significantly more pure SCLC (P = 0.04), more lymphatic invasion (P = 0.03) and more relapse (P = 0.04) than the low‐expression subgroup. The knockdown of HOTAIR in SBC‐3 cells led to decreased proliferation activity and decreased invasiveness in vitro. Gene expression analysis indicated that depletion of HOTAIR resulted in upregulation of cell adhesion‐related genes such as ASTN1, PCDHA1, and mucin production‐related genes such as MUC5AC, and downregulation of genes involved in neuronal growth and signal transduction including NTM and PTK2B. Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target.