WEE1 Confers Resistance to KRAS Inhibitors in Non-Small Cell Lung Cancer.

KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

Predictors of nodal upstaging in clinical N1 nonsmall cell lung cancer.

Background: Surgical resection followed by adjuvant chemotherapy is currently the first choice for the treatment of clinical N1 (cN1) non-small cell lung cancer (NSCLC). However, diagnosing cN1 correctly can be difficult, even with current imaging diagnostic technologies. We aimed to analyze the diagnostic accuracy of preoperative nodal status and the predictive factors for nodal upstaging of cN1-NSCLC.

Protocol summary of a randomized phase III study: comparing systemic therapy with and without debulking surgery (primary tumour resection) for clinical stage IVA (cT1-2bN0-1M1a) non-small cell lung cancer with radiologically undetermined pleural dissemination JCOG2103 (DEBULK-LUNG).

In patients with non-small cell lung cancer (NSCLC) who present with radiologically undetermined malignant pleural dissemination or incidental surgical diagnosis of the same, surgery is generally not the preferred option; systemic therapy is favoured. However, there is no consensus on incorporating primary site resection into the treatment plan. Retrospective analyses hint at potential benefits of combining systemic therapy with primary site resection, but prospective studies have yet to confirm these findings.

Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour.

Aims: The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours TFE3 fusion; however, YAP1::TEE3 has not been reported. Clear cell stromal tumour of the lung (CCST-L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and YAP1::TFE3 fusion.

Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.

Background: The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease.

Oncofetal IGF2BP3-mediated control of microRNA structural diversity in the malignancy of early-stage lung adenocarcinoma.

The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion.

Updated review of perioperative treatment for non-small-cell lung cancer in the new era of immune checkpoint inhibitors: past, present, and future.

The perioperative treatments for non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the survival of patients with NSCLC who underwent surgical resection alone has been dismal except in stage IA patients. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant cisplatin-based chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy.

Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010.

Background: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung.

Methods: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.

Background: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed.

Methods: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC.

Results: Of the patients included, 99 (50.

Oncological feasibility of segmentectomy for inner-located lung cancer.

Objective: Oncological feasibility of segmentectomy for internal non-small cell lung cancer (NSCLC) has not been assessed adequately. We assessed the oncological feasibility of segmentectomy for inner-located NSCLC by investigating surgical margins and patient prognosis after undergoing the procedure.

Methods: Of the 3555 patients who underwent resection for lung cancer between 2013 and 2019 at our institution, 659 patients who underwent segmentectomy for clinical stage 0 to stage1A NSCLC were included in this study.

Quantitative identification of causes of instrumental acoustic signal distortion in Global Navigation Satellite System-Acoustics Combination observations.

The Seafloor Geodetic Observation-Array (SGO-A), operated by the Japan Coast Guard, relies on the Global Navigation Satellite System-Acoustics combination (GNSS-A) technique, which integrates satellite positioning systems and undersea acoustic ranging to determine seafloor crustal deformation at the centimeter level for earthquake disaster prevention. Recently, we found distortion in the SGO-A 10-kHz carrier wave that degraded the accuracy. Carrier wave distortion can cause errors on the scale of several centimeters to twenty centimeters, which greatly impedes centimeter-level observations.

Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

Purpose: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe.

Methods: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010.

An algorithm-based technique for counting mitochondria in cells using immunohistochemical staining of formalin-fixed and paraffin-embedded sections.

Purpose: Visualizing mitochondria in cancer cells from human pathological specimens may improve our understanding of cancer biology. However, using immunohistochemistry to evaluate mitochondria remains difficult because almost all cells contain mitochondria and the number of mitochondria per cell may have important effects on mitochondrial function. Herein, we established an objective system (Mito-score) for evaluating mitochondria using machine-based processing of hue, saturation, and value color spaces.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groups in the Forthcoming (Ninth) Edition of the TNM Classification for Lung Cancer.

Introduction: The TNM classification of lung cancer is periodically revised. The International Association for the Study of Lung Cancer collected and analyzed a new database to inform the forthcoming ninth edition of the TNM classification. The results are herewith presented.

Passive Smoking-Induced Mutagenesis as a Promoter of Lung Carcinogenesis.

Introduction: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a group 1 carcinogen linked to lung cancer. However, in contrast to active smoking, the mutagenic properties of PS remain unclear.

Methods: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared.