Skip to main content

Malignant pleural effusion in NSCLC, molecular pathogenesis, and management strategies maintaining the pipes

Sara Salah1, Mohyeldin S Abdelhalim2, Waleed Arafat3

Author Email This email address is being protected from spambots. You need JavaScript enabled to view it.

Introduction: Malignant pleural effusion (MPE), known as cancer cells reaching the pleural space, usually indicates the presence of advanced disease. Lung cancer is a major contributing cause for malignant pleural effusion (MPE). Treatment is mainly fixed on addressing the palliative measures and improving the patient’s symptoms without providing any radical solution to the primary pathogenesis of the disease

Aim: To utterly understand the mechanism of metastasis and cancer progression in the case of MPE, it should be stated that in normal conditions, cells are consistently subjected to physical forces affecting the function as well as the phenotype of cells. These forces apply active or passive mechanical stress to all cells responsible for the hemodynamic stability of lung inflation and vascular perfusion. A variety of forces can apply such pressure on lung parenchymal cells and in different forms like changes in stress or strain and shear stress.

Method: The cellular response to these forces is purely the function of intracellular signaling that enables the cell to communicate the information to its interior. Mechanotransduction simply implies the transformation of the mechanical induced changes into biochemical signals which eventually alter gene expression and cell fate. Malignant transformation implies errors in the mechanotransduction pathway that leads to aberrant cellular behavior and the activation of key signaling pathways that drive phenotypical switching into more mesenchymal-like cancer cells from normal cells. Malignant cells promote the EMT with loss of the E-cadherin proteins which allow cells to escape into spaces or other sites. E-cadherin mutations have been strongly correlated with the EGFR pathway. Realignment of E-cadherin through histone deacetylases has led to enhanced sensitivity of the resistant NSCLC cell lines to gefitinib. Acquired resistance to gefitinib or osimeritinib in NSCLC cells has been correlated with the expression of EMT. In-addition, Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) play an important role in the mechanotransduction process. YAP/TAZ are regulators of the transcription process, and they are the key master of the Hippo signaling pathway. It has been linked to not only the pathogenesis of lung cancer but also to the progression of the tumor and its metastasis.

Results: Finally, Novel modalities targeting the mechanotransdution process is currently pioneering the field of research.

Conclusion: More in-depth analysis is urgently needed and targeting the mechanotransduction mechanism and tumor micro-environment may play a major role in the near future.