Lung cancer with comorbid interstitial pneumonia: Current situation and animal model development

Interstitial pneumonia includes a range of disorders affecting the lung interstitium, significantly impacting life expectancy, especially during acute exacerbations. Concurrently, lung cancer remains a leading cause of cancer-related deaths worldwide. The coexistence of these two conditions presents a formidable challenge, complicating diagnosis, treatment, and prognosis. This review explores the critical issues associated with lung cancer comorbid with interstitial pneumonia, focusing on diagnostic challenges, prognosis, treatment complications, and the lack of effective research tools. Diagnosing lung cancer in patients with interstitial pneumonia is complicated due to overlapping imaging features and the risks associated with biopsies. The prognosis is poorer for patients with both conditions, as interstitial pneumonia promotes a more aggressive lung cancer phenotype. Standard treatment for interstitial pneumonia can inadvertently facilitate lung cancer progression, while anticancer therapies often exacerbate interstitial pneumonia. To address the lack of appropriate research tools, a novel murine model combining orthotopic lung cancer cell transplantation with bleomycin-induced interstitial pneumonia was developed to better understand their interaction. This new murine model successfully mimics the human condition, demonstrating increased tumor growth, metastasis, and alterations in the tumor microenvironment, including elevated tumor-associated macrophages, cancer-associated myofibroblasts, and regulatory T cells, alongside decreased cytotoxic T lymphocytes. Lung cancer comorbid with interstitial pneumonia represents a severe clinical challenge due to diagnostic difficulties and treatment-related complications. The novel murine model offers a valuable tool for future research to develop effective therapies. Dedicated efforts are needed to address this complex pathophysiology to improve patient outcomes.