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Molecular pathology of lung cancer: current status and perspectives

Purpose of review In this article, we summarize the current knowledge on molecular alterations in lung cancer that are targets for therapy, and provide an outlook on the future development of molecular pathology in precision oncology. Recent findings Lung cancer has become a paradigm for the success of molecular targeted therapies in solid tumors. Tyrosine kinase inhibitors are effective treatment options in adenocarcinoma patients with an EGFR, ALK, ROS1 or B-Raf Proto-Oncogene, Serine/Threonine kinase mutation. Additional molecular targets that are addressed in clinical trials include ERBB2, MET, RET, NTRK1 and FGFR. Therapies with antibodies that block the interaction of PD-L1 with PD-1 and thereby liberate an antitumor immune response have introduced a new era in cancer therapy with impressive therapeutic benefits. The high financial burden, treatment failures and therapeutic side effects of immunotherapies have prompted a search for biomarkers beyond PD-L1 expression, for example, tumor mutation load or immune cell profiling, that might more reliably identify patients that are likely to respond. Summary The discoveries of cancer research have been translated into the clinical management of lung cancer patients. So far, the approach of targeted therapy that is directed towards certain molecular alterations in a given tumor has been successful for adenocarcinomas, but not yet for squamous or small cell carcinomas. Further clinical progress will require a better und...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research

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ConclusionHER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsYoung patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
In this study, we investigated the functional role and prognostic value of spindle pole body component 25 (SPC25) in non-small cell lung cancer (NSCLC). SPC25 expression profile in lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and normal lung tissues was examined by using data from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). LUAD A549 cells and LUSC H520 cells were used to investigate the influence of SPC25 on cancer stem cell (CSC) properties in terms of the proportion of CD133+ cells, tumorsphere formation and CSC markers, including CD133, ALDH1 and Sox2. Data mining was also perfo...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
ABSTRACT A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision‐cut slices from Kras‐driven non‐small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates that signaling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma (ASC), and MAPK activity in adenocarcinoma (AC). In addition, high inter‐ and intra‐tumor variability i...
Source: The Journal of Pathology - Category: Pathology Authors: Tags: Original Paper Source Type: research
AbstractWe previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb‐b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti‐ERBB2 therapeutic agents may be effective for ERBB2‐mutant cancers. The familial lung cancer patient in one of the authors’ institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhi...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine, Precision Medicine Clinic: Molecular Tumor Board Source Type: research
Conclusions Patient demographics and socioeconomic status are associated with the decision to perform MLNE. Thoracic surgeons should access these factors and perform MLNE to accurately determine tumor stage and improve survival.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Conclusions TAP73 mRNA expression significantly increased in cancer tissues than cancer-adjacent tissues in all NSCLC patients and in patients with adenocarcinoma. Meanwhile, the fold-change of DNP73/TAP73 ratio was similar to TAP73. MDM2 protein expression significantly increased in cancer tissues in female NSCLC patients.
Source: Revista Portuguesa de Pneumologia - Category: Respiratory Medicine Source Type: research
CONCLUSIONS: Our results suggest that DWI parameters (minimum ADC and normalized ADC ratio) for the solid components of brain metastasis from lung cancer are not correlated with their histology, whereas they can predict the EGFR mutation status in brain metastasis from lung adenocarcinoma.
Source: American Journal of Neuroradiology - Category: Radiology Authors: Tags: ADULT BRAIN Source Type: research
CONCLUSION: A comparative analysis was also carried out on related transcriptomic datasets, which indicates that the proposed biomarkers provide discerning power for accurate stage prediction, and will be improved when larger-scale proteomic quantitative technologies become available. PMID: 29424557 [PubMed - as supplied by publisher]
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
Authors: Kunal S, Jain S, Shah A Abstract Lepidic adenocarcinoma previously known as bronchioloalveolar carcinoma (BAC) is a non-small cell lung cancer with an indolent presentation. Bronchial anthracofibrosis (BAF) is caused by long-standing exposure to biomass fuel smoke often in poorly ventilated kitchen. Middle lobe syndrome (MLS) due to BAF is not uncommon however, lepidic adenocarcinoma then known as BAC, presenting as MLS has been documented only once before in the Polish literature. A 68-year-old never-smoker female with biomass fuel smoke exposure presented with cough and breathlessness. Imaging revealed M...
Source: Monaldi Archives for Chest Disease - Category: Respiratory Medicine Tags: Monaldi Arch Chest Dis Source Type: research
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