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Improved treatment for people with advanced lung cancer
Researchers have now investigated which patients with lung cancer should be treated with nintanib and why the drug is ineffective in people with squamous cell carcinoma.
In the current study by the University of Barcelona, the researchers made great progress in treating advanced lung cancer. The results of the study were published in the English-language journal "Cancer Research".
Nintanib is ineffective in squamous cell carcinoma
The researchers tried to improve the effectiveness of nintanib, a drug used to treat lung cancer. The team identified molecular mechanisms underlying the drug's ineffectiveness in squamous cell carcinoma, a subspecies of non-small cell lung cancer.
Study could lead to new therapeutic strategies
The results obtained could have an impact on the design of new therapeutic strategies to extend the clinical benefit of the drug to a wider range of people with lung cancer.
How does nintanib work?
The mechanism of action of nintanib is based on the inhibition of receptors that are involved in the formation of new vessels (angiogenesis) and fibrosis that drive tumor progression. Previous studies reported that this drug is effective for treating advanced lung adenocarcinoma, but not for treating squamous cell carcinoma.
Researchers examined differences between subtypes of lung cancer
In order to identify the causes of the differences between the two main subtypes of non-small cell lung cancer, the new study analyzed tumor fibrosis (chronic tissue scarring) and the response to antifibrotic treatment with nintanib in cells and tissue samples from people with lung cancer.
People with adenocarcinoma respond better to treatment with nintedanib
Preclinical cell culture models were used in the study, which enable the interaction between the two most common cells within a tumor: cancer cells and fibroblasts. The results show for the first time that tumor fibrosis is higher in adenocarcinoma than in squamous cell carcinoma, which means that patients with adenocarcinoma respond better to treatment with nintedanib.
Why did people respond better to treatment?
The researchers also identified the underlying mechanism: the pro-fibrotic transcription factor SMAD3 in fibroblasts is more epigenetically displaced in squamous cell carcinoma than in adenocarcinoma, which leads to less fibrosis in those with squamous cell carcinoma and makes them resistant to nintanib.
Smoking reduces the success of treatment
The study also identified the key role of smoking and the associated ineffectiveness of the drug against squamous cell carcinoma. Cigarette smoke particles change the SMAD3 gene epigenetically. This ultimately reduces its activity and increases resistance to the drug. The results of the study could have a major impact on the development of therapeutic strategies for the treatment of adenocarcinomas with different drug combinations.
Which people particularly benefit from nintedanib?
Since fibrosis is a common side effect caused by radiation therapy toxicity, the results suggest that those who receive radiation therapy for adenocarcinoma (especially non-smokers) may benefit most from antifibrotic drugs such as nintedanib.
Treatment of adenocarcinoma with nintedanib
Fibrosis is associated with immunosuppression and tumor growth, so the results support that adenocarcinoma sufferers may benefit from combining antifibrotic drugs such as nintedanib with immunotherapy. (as)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
- Rafael Ikemori, Marta Gabasa, Paula Duch, Miguel Vizoso, Paloma Bragado et al .: Epigenetic SMAD3 repression in tumor-associated fibroblasts impairs fibrosis and response to the antifibrotic drug nintedanib in lung squamous cell carcinoma, in Cancer Research (query: 20.11.2019 ), Cancer Research