Lung Cancer Proteogenomics: Shaping the Future of Clinical Investigation.

BACKGROUND: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. METHODS: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. RESULTS: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. CONCLUSIONS: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer.

Postpneumonectomy-like syndrome due to bronchial carcinoid: a unique case report.

BACKGROUND: Postpneumonectomy-like syndrome is a rare condition resulting from unilateral lung disease with severe lung volume loss leading to excessive mediastinal shift and herniation of the healthy lung into the contralateral hemithorax, mimicking the mediastinal shift observed in postpneumonectomy syndrome after pneumonectomy. We report a unique case of postpneumonectomy-like syndrome caused by an atypical bronchial carcinoid completely occluding the left main bronchus. CASE PRESENTATION: A 25-year-old woman presented with symptoms of chronic exertional dyspnea and productive cough. Imaging studies showed complete left lung atelectasis due to a mass occluding the left main bronchus, as well as extreme mediastinal deviation and substantial herniation of the right lung into the left hemithorax. Bronchoscopic biopsy of the tumor and subsequent left pneumonectomy with concurrent lymph node dissection revealed an atypical carcinoid. Sixteen months after surgery the patient has been asymptomatic with repeat imaging studies showing no change in mediastinal shifting. CONCLUSION: Bronchial carcinoids are notorious for causing bronchial obstruction. The present case represents an extreme complication of centrally located bronchial carcinoid, resulting in postpneumonectomy-like syndrome with severe mediastinal shift and herniation of the healthy lung into the diseased hemithorax.

Sarcoidosis-Like Reactions Induced by Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are a newly developed component of cancer care that expands the treatment possibilities for patients. Their use has been associated with several immune-related adverse events, including ICI-induced sarcoidosis-like reactions. This article reviews the data concerning ICI-induced sarcoidosis-like reactions currently available in the medical literature. These reactions have been reported in three classes of ICIs: anti-cytotoxic T-lymphocyte associated protein 4 antibodies, programmed death 1 inhibitors and programmed death ligand 1 inhibitors. These reactions are indistinguishable from sarcoidosis with a similar histology, pattern of organ involvement, and pattern of clinical manifestations. The most common locations to observe granulomatous inflammation from these reactions is in intrathoracic locations (the lung and/or mediastinal lymph nodes) and the skin. The median time between initiation of an ICI and the development of a sarcoidosis-like reaction averaged 14 weeks. Clinicians have opted to use corticosteroids and/or discontinue the ICI, or take no action when these reactions have developed. Regardless of whether the clinician performed an intervention or not, these reactions have uniformly improved or resolved after ICI-treatment, which provides additional temporal evidence supporting the presence of a sarcoidosis-like reaction as opposed to sarcoidosis. There is even evidence that the development of an ICI-induced sarcoidosis-like reaction suggests that the ICI is effective as an anti-tumor agent and should be continued. As is the case for sarcoidosis, sarcoidosis-like reactions do not mandate antisarcoidosis therapy, especially if the condition is asymptomatic. When treatment of sarcoidosis-like reaction is required, it may be prudent to continue ICI therapy and add antisarcoidosis therapy because standard antisarcoidosis regimens seem to be effective. Further research into the mechanisms involved in the development of ICI-induced sarcoidosis-like reactions may give insights into the immunopathogenesis of sarcoidosis.