A Case of ALK‐Rearranged Combined Lung Adenocarcinoma and Neuroendocrine Carcinoma with Diffuse Bone Metastasis and Partial Response to Alectinib

We report a rare case of stage IV pulmonary combined large-cell neuroendocrine carcinoma
(LCNEC) and adenocarcinoma (ACA), both demonstrating anaplastic lymphoma kinase (ALK)
rearrangement by IHC and FISH. This 61-year-old lifelong nonsmoking Asian woman presented with
a cough, and after diagnosis and surgical treatment, completed four cycles of adjuvant cisplatin and
etoposide chemotherapy. She subsequently developed recurrence with bony metastases of exclusively
ALK-positive LCNEC. Alectinib was started, and the patient experienced a partial response READ ARTICLE

Current Oncology DOI:10.3390/curroncol29020072

Authors: Chloe A. Lim, Norbert Banyi, Tracy Tucker, Diana N. Ionescu, Barbara Melosky

Case StudyKirk SmithFebruary 3, 2022neuroendocrine, adenocarcinoma, driver mutation, ALK, LCNEC

Significance of TP53 Mutation in Cellular Process and Disease Progression in Lung Adenocarcinoma

Analysis of the TCGA data showed TP53 mutations in 22% of LUAD patients. Clinicopathological analyses demonstrated that TP53 mutation was correlated with the disease progression but not prognosis. We identified 1935 differentially expressed genes (DEGs). Functional enrichment analysis showed that the DEGs were mainly concentrated in metabolism, cell differentiation, and cancer-related pathways. The top hub genes were identified and disease analysis revealed the most critical genes related to disease progression and prognosis. The expression levels of several of these genes were then tested in tumor tissues. Our results showed that TP53 mutation plays a critical role in cellular process and the clinicopathological findings in LUAD. We also identified potential key genes, which could provide novel evidence for individualized treatment. READ ARTICLE

Genetic Testing and Molecular Biomarkers DOI:10.1089/gtmb.2020.0304

Authors: Yongbo Hou, Sheng Tan, Guoxiang Wang

Real-World OutcomesKirk SmithMay 1, 2021TP53, adenocarcinoma, lung

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Summary: To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification ..... READ ARTICLE

Cell DOI:10.1016/j.cell.2020.06.013

Authors: Michael A. Gillette, Shankha Satpathy, Song, Cao,.. AND MANY MORE

"Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer with ALK Rearrangement"

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint
inhibitor (ICI) treatment e cacy. The clinical e cacy of ICIs for non-small-cell lung cancer (NSCLC)
patients harboring major mutations, such as EGFR or ALK mutations, is limited. We genotyped
190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab
monotherapy, and examined the e cacy in NSCLC patients with or without major mutations.
Among the patients enrolled in the genotyping study, 47 patients harbored EGFR mutations, 25 patients
had KRAS mutations, 5 patients had a HER2 mutation, 6 patients had a BRAF mutation, and 7 patients
had ALK rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the
rate of high PD-L1 expression ( 50%) was significantly higher in patients with ALK mutations.
The progression-free survival was 0.6 (95% CI: 0.2–2.1) months for ALK-positive patients and 1.8 (95%
CI: 1.2–2.1) months for EGFR-positive patients. All patients..... READ ARTICLE

International Journal of Molecular Sciences DOI:10.3390/ijms21072623

Authors: Yuko Oya, Hiroaki Kuroda, Takeo Nakada, Yusuke Takahashi, Noriaki Sakakura, Toyoaki Hida

Transformation of EML4-ALK fusion-positive adenocarcinoma into squamous cell carcinoma in association with acquired resistance to crizotinib

The development of targeted therapies has revolutionized the treatment of patients with lung cancer, especially non-small-cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) is a research hotspot of molecular targeted therapy for lung cancer. ALK tyrosine kinase inhibitors (TKIs) are highly effective for ALK-rearranged NSCLC-positive patients. These targeted therapies have significant clinical effects; however, they inevitably lead to acquired resistance. In previous studies, the histological transformation after ALK inhibitor treatment was mostly based on small-cell lung cancer (SCLC). The transformation from adenocarcinoma into squamous cell carcinoma in NSCLC after treatment with ALK TKI was extremely rare. This study aimed to report a case of lung cancer with a histological transformation from adenocarcinoma into squamous cell carcinoma after crizotinib treatment, still having the original ALK rearrangement at the molecular level. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.01.001

Authors: Fenfang Wang, Jing Qin, Fajun Xie, Qihuan Wu, Hongyang Lu

Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study

Objective The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is a key oncogenic driver in non-small cell lung cancer (NSCLC). This study analyzed the clinicopathological characteristics and prognostic significance of EML4-ALK fusion gene in patients with surgically resected adenocarcinoma. Methods The clinicopathological characteristics of 1056 consecutive patients with surgically resected stage I–IIIA adenocarcinoma were collected from February 2014 to October 2014, and EML4-ALK rearrangement was detected using real-time polymerase chain reaction (RT-PCR) technology. To compare the imaging and pathological features, a propensity score matching (PSM) method was performed. The follow-up information was collected to evaluate the long-term outcomes of patients with EML4-ALK rearrangement. Results The prevalence of EML4-ALK rearrangement was 6.6% in 1056 consecutive patients. A total of 70 EML4-ALK-positive and 210 EML4-ALK-negative patie..... READ ARTICLE

Cancer management and research DOI:10.2147/CMAR.S229217

Authors: Shi J, Gu W, Zhao Y, Zhu J, Jiang G, Bao M, Shi J.