Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Climatic control of denudation in the deglaciated landscape of the Washington cascades

Since the Last Glacial Maximum, the extent of glaciers in many mountainous regions has declined, and erosion driven by glacial processes has been supplanted by fluvial incision and mass wasting processes. This shift in the drivers of erosion is thought to have altered the rate and pattern of denudation of these landscapes. The Washington Cascades Mountains in the northwestern USA still bear the topographic imprint of Pleistocene glaciations, and are affected by large variations in precipitation, making them an ideal setting to assess the relative controls of denudation. Here we show that denudation rates over the past millennia, as determined by 10Be exposure ages, range from 0.08 to 0.57 mm yr−1, about four times higher than the rates inferred for million-year timescales. We find that the millennial timescale denudation rates increase linearly with modern precipitation rates. Based on our landscape analyses, we suggest that this relationship arises because intense precipitation triggers landslides, particularly on slopes that have been steepened by glacial erosion before or during the Last Glacial Maximum. We conclude that the high modern interglacial denudation rates we observe in the Washington Cascades are driven by a disequilibrium between the inherited topography and the current spatial distribution of erosional processes that makes this range particularly sensitive to spatial variations in climate