Pulmonary Comorbidity in Lung Cancer

Abstract

Pulmonary hypertension (PH) is caused by many disorders that affect the pulmonary vasculature. A recent study has provided evidence that pulmonary vascular remodeling and PH can be observed in lung cancer, and this may be associated with tumor cell-immune cell inflammatory crosstalk. These findings highlight the pressing need to understand better and manage pulmonary vascular comorbidities in lung cancer.

Keywords: cardio-oncology; disease comorbidity; inflammatory; lung cancer; pulmonary hypertension.

Figure 1. Lung Cancer-associated Pulmonary Hypertension

Diagram illustrating the biological hypothesis of lung cancer-associated pulmonary hypertension (PH). Lung cancer may trigger pulmonary comorbidities by tumor cell-immune cell inflammatory cross-talk (e.g. macrophages; lymphocytes), mediated in part, by the up-regulation of phosphodiesterase-5 (PDE5 [a well-known downstream protein involving in PH pathogenesis]) and the release of several cytokines and chemokines (e.g., interleukin-8 [IL-8] and granulocyte macrophage colony stimulating factor [GM-CSF]) that can promote vascular remodeling. This cross-talk is illustrated by the comorbid disease module between the lung cancer and pulmonary hypertension in the human protein-protein interactome. Potential actionable biomarkers for patient stratification and personalized treatment in patients with lung cancer and pulmonary comorbidities might be identified using the human interactome network. A combination of sildenafil (a known PDE5 inhibitor) and existing targeted cancer therapeutic agents might potentially improve vascular remodeling, and presumably, provide therapeutic benefit for lung cancer patients with PH comorbidities.