Williams Cancer Institute

Breaking Ground in Lung Cancer Treatment: Targeting Tumor-Fibroblast Interactions

 

Fibroblasts play a crucial role in building and maintaining the extracellular matrix, providing structural support for cells in connective tissues throughout the body. However, recent research suggests that cancerous tumors can manipulate nearby fibroblasts to their advantage, fueling their growth and making them more invasive. This phenomenon, known as cancer-associated fibroblast activation, poses a significant challenge in cancer treatment, as it can also render tumors resistant to chemotherapy.

A groundbreaking study conducted by researchers from Academia Sinica, National Yang Ming Chiao Tung University, National Taiwan University Hospital, and National Taiwan University has shed light on a potential breakthrough in lung cancer treatment. Published in APL Bioengineering, the study introduces a novel 3D cell culture system designed to investigate how inhibiting fibroblast activity could enhance the efficacy of anti-cancer drugs, particularly in lung cancer.

Lead author Chau-Hwang Lee emphasizes the urgent need for innovative strategies to combat lung cancer metastasis, which is responsible for nearly 90% of patient deaths in late-stage cases. By simulating the tumor microenvironment and creating a lifelike tissue model, the research team co-cultured lung cancer cells with fibroblasts within a 3D matrix. This setup enabled them to observe the interactions between cancer cells and fibroblasts, mimicking the complexities of real tumors more accurately.

The study focused on evaluating the combination of the anti-fibrotic drug nintedanib with the conventional anti-cancer drug cisplatin. Results revealed that nintedanib significantly enhanced the anti-cancer effects of cisplatin, while another anti-fibrotic drug, pirfenidone, did not exhibit a similar effect. This finding suggests that targeting fibroblast activity alongside conventional chemotherapy could offer a promising treatment approach for lung cancer patients.

Pirfenidone is a drug primarily used to treat idiopathic pulmonary fibrosis (IPF), a chronic and progressive lung disease that causes scarring and hardening of lung tissues. Pirfenidone works by reducing the formation of scar tissue in the lungs, which can help slow down the progression of the disease and improve symptoms in some patients. Its use is also being investigated in other fibrotic diseases, such as pulmonary fibrosis associated with scleroderma and liver fibrosis.

The development of this 3D cell culture system marks a significant advancement in cancer research, providing a more reliable alternative to animal testing for assessing drug efficacy and safety. Beyond lung cancer, the system holds promise for studying other solid tumors and exploring potential treatment strategies. The authors plan to expand their research to include other cancer types, such as liver and oral cancer, while refining the culture system to better replicate the tumor microenvironment.

In conclusion, this study opens new avenues for the development of more effective treatment options for lung cancer and other solid tumors. By targeting tumor-fibroblast interactions, researchers aim to improve patient outcomes and introduce innovative tools for preclinical drug testing, ultimately advancing the fight against cancer.

The article, authored by Huei-Jyuan Pan, Chia-Wei Lee, Li-Yu Wu, Heng-Hua Hsu, Yi-Chung Tung, Wei-Yu Liao, and Chau-Hwang Lee, will be published in APL Bioengineering on March 28, 2023.

Reference: Pan, H.-J., Lee, C.-W., Wu, L.-Y., Hsu, H.-H., Tung, Y.-C., Liao, W.-Y., & Lee, C.-H. A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts. https://pubs.aip.org/aip/apb/article/7/1/016117/2879098/A-3D-culture-system-for-evaluating-the-combined

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