Lung cancer: when radiation therapy fails

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On the left is stained adenocarcinoma of the lung. Enlarged section B shows healthy lung tissue, enlarged section C shows adenocarcinoma. Section D shows a PET-CT scan of a metabolically active central lung tumor close to the trachea, heart, and esophagus. The radiation dose distribution is shown in color: the desired dose is 100% in the tumor and 80% in the extended tumor area. 25% and 10% of radiation dose (turquoise and blue lines) to healthy tissue for technical reasons. Credit: Oliver Hartman, JMU / Thomas Fisher, UK

Lung cancer is the most common cancer in the world, with 2.2 million new cases and about 1.8 million deaths in 2020 alone. Although knowledge of the disease has greatly improved and new therapeutic strategies can prolong the lives of previously incurable patients, the numbers clearly show that lung cancer is still a serious disease and the death rate is still too high.

New and improved treatments are needed to further reduce the number of deaths from this type of tumor. Würzburg researchers are focused on radiation therapy. In combination with chemotherapy, it is still one of the most important treatment approaches. This is especially relevant for late stages of non-small cell lung tumors, where treatment options are quite limited.

PTEN mutation is suitable as a biomarker

With this type of lung tumor, radiation therapy may not be effective. This is due to the interaction of a common, specific mutation in the PTEN gene with the DNA repair enzyme ATM, as the Würzburg team found.

However, lung tumors in which this mutation occurs can be therapeutically affected. With the help of two experimental inhibitors, the researchers managed to block the DNA repair enzyme in tumor cells. As a result, tumors became sensitive to radiation again and could be killed in tumor models.

Inhibitors in preclinical trials

“Such inhibitors are not yet approved for use in humans, but are participating in clinical trials,” explains cancer researcher Dr. Markus Dieffenbacher from the Biocenter of the University of Würzburg. His team published the new results in the journal Cell and Biological Sciences together with a team led by radiation therapist Dr. Thomas Fischer from Professor Michael Flentier’s research group at the University Hospital of Würzburg.

If inhibitors are undergoing clinical trials, they offer a new possibility: the PTEN mutation is suitable as a biomarker that indicates tumor resistance to radiation. With the help of appropriate tests, it would be possible to precisely identify patients who might benefit from a combination of inhibitors and radiation therapy. It could be implemented quickly: patients with non-small cell lung cancer are already routinely screened for PTEN and other disease-associated mutations.

Focus on reducing the radiation dose

Currently, several clinical trials review the impact of PTEN and ATM on treatment outcomes. “We are confident that our new findings will generate great interest in the implementation of this innovative strategy for the treatment of non-small cell lung tumors,” says Professor Michael Flentje.

Radiation therapy is the main method of treatment for tumors of the respiratory tract and other organs in the late stages. Therefore, the Würzburg team continues to explore new strategies and goals. One focus is on reduction radiation dose in such a way that the desired therapeutic success is still achieved and at the same time healthy tissue around the tumor is preserved as much as possible.


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Additional information:
Thomas Fisher et al., PTEN-mutant non-small cell lung cancer requires ATM to suppress proapoptotic signaling and evade radiation therapy, Cell and Biological Sciences (2022). DOI: 10.1186/s13578-022-00778-7

Citation: Lung Cancer: When Radiation Therapy Doesn’t Work (2022, July 5) Retrieved July 5, 2022, from https://medicalxpress.com/news/2022-07-lung-cancer-radiotherapy.html

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