Somatic Mutations in Normal Tissues: Calm before the Storm.

We explore the phenomenon of somatic mutations, including those in cancer driver genes, that are present in healthy, normal-appearing tissues and their potential implications for cancer development. We also examine the landscape of these somatic mutations, discuss the role of clonal cell competition and external factors like inflammation in enhancing the fitness of mutant clones, and conclude by considering how understanding these mutations will aid in prevention and/or interception of cancer.

An atlas of epithelial cell states and plasticity in lung adenocarcinoma.

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers.

Beyond bacteria: How the intratumor mycobiome modulates lung adenocarcinoma progression.

Increasing evidence suggests that tumors harbor diverse microbiomes, adding complexity to the tumor microenvironment. In this issue of Cancer Cell, Liu et al. highlight the role of the intratumor mycobiome, specifically Aspergillus sydowii, in promoting lung adenocarcinoma progression.

Pathogenesis of Tobacco-Associated Lung Adenocarcinoma Is Closely Coupled with Changes in the Gut and Lung Microbiomes.

Microbial dysbiosis has emerged as a modulator of oncogenesis and response to therapy, particularly in lung cancer. Here, we investigate the evolution of the gut and lung microbiomes following exposure to a tobacco carcinogen. We performed 16S rRNA-Seq of fecal and lung samples collected prior to and at several timepoints following (nicotine-specific nitrosamine ketone/NNK) exposure in mice that were previously shown to exhibit accelerated lung adenocarcinoma (LUAD) development following NNK exposure.

Cell-by-Cell: Unlocking Lung Cancer Pathogenesis.

For lung cancers, cellular trajectories and fates are strongly pruned by cell intrinsic and extrinsic factors. Over the past couple of decades, the combination of comprehensive molecular and genomic approaches, as well as the use of relevant pre-clinical models, enhanced micro-dissection techniques, profiling of rare preneoplastic lesions and surrounding tissues, as well as multi-region tumor sequencing, have all provided in-depth insights into the early biology and evolution of lung cancers. The advent of single-cell sequencing technologies has revolutionized our ability to interrogate these same models, tissues, and cohorts at an unprecedented resolution.

Game of clones: Battles in the field of carcinogenesis.

Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of "field cancerization", that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium. Making sense of those mutations to understand the progression along the pathologic continuum of normal epithelia, preneoplasias, up to malignant tissues will help pave way for identification of ideal targets that can guide new strategies for preventing or eliminating cancers at their earliest stages of development.

Chronic Exposure to Waterpipe Smoke Elicits Immunomodulatory and Carcinogenic Effects in the Lung.

Unlabelled: Effects of waterpipe smoking on lung pathobiology and carcinogenesis remain sparse despite the worldwide emergence of this tobacco vector. To address this gap, we investigated the effects of chronic waterpipe smoke (WPS) exposure on lung pathobiology, host immunity, and tumorigenesis using an experimental animal model that is prone to tobacco carcinogens and an exploratory observational analysis of human waterpipe smokers and nonsmokers. Mice exhibited elevated incidence of lung tumors following heavy WPS exposure (5 days/week for 20 weeks) compared to littermates with light WPS (once/week for 20 weeks) or control air.

Cancer in Lebanon: A Review of Incidence Rates from 2008 to 2015 and Projections Till 2025.

 Cancer carries one of the heaviest burdens globally in terms of mortality. Lebanon is a middle-income Middle East country also plagued with cancer, as such a study and analysis of cancer trends and projections would serve a great benefit in the fight against the disease.  All data pertaining to cancers in Lebanon were extracted from the National Cancer Registry of Lebanon Web site.

Augmented Lipocalin-2 Is Associated with Chronic Obstructive Pulmonary Disease and Counteracts Lung Adenocarcinoma Development.

Early pathogenesis of lung adenocarcinoma (LUAD) remains largely unknown. We found that, relative to wild-type littermates, the innate immunomodulator (lipocalin-2) was increased in normal airways from mice with knockout of the airway lineage gene () and that are prone to developing inflammation and LUAD. Yet, the role of LCN2 in lung inflammation and LUAD is poorly understood.

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment.

Lung cancer is the number one cause of cancer-related deaths. The malignancy is characterized by dismal prognosis and poor clinical outcome mostly due to advanced-stage at diagnosis, thereby inflicting a heavy burden on public health worldwide. Recent breakthroughs in immunotherapy have greatly benefited a subset of lung cancer patients, and more importantly, they are undauntedly bringing forth a paradigm shift in the drugs approved for cancer treatment, by introducing "tumor-type agnostic therapies".

Epigenetic Suppression of the T-box Subfamily 2 () in Human Non-Small Cell Lung Cancer.

(1) The subfamily of transcription factors (s 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the subfamily in human NSCLC.

Genomics of adult and pediatric solid tumors.

Different types of cancers exhibit disparate spectra of genomic alterations (germline and/or somatic). These alterations can include single nucleotide variants (SNVs), copy number alterations (CNAs) or structural changes (e.g.

Smoking and Lung Cancer: A Geo-Regional Perspective.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) represents the most frequently diagnosed subtype of this morbid malignancy. NSCLC is causally linked to tobacco consumption with more than 500 million smokers worldwide at high risk for this fatal malignancy.