Drug May Make Mesothelioma Cells More Sensitive to Radiation

Scottish cancer researchers say they have found a way to make mesothelioma cells more sensitive to radiation. 

Radiotherapy is one of the tools doctors can use to help slow progression of the asbestos cancer. It can also help alleviate mesothelioma symptoms. 

But proteins expressed by mesothelioma cells can make them less sensitive to radiation. The Glasgow-based research team is getting around this protection with a sensitizing drug. The drug mimics a process that already happens in healthy people.

Radiotherapy in the Treatment of Mesothelioma

Radiotherapy is not usually the primary treatment for malignant mesothelioma. Most mesothelioma patients have chemotherapy as their first-line treatment. 

But newer technology means that radiation can be more targeted than it used to be. This means that healthy cells – which are more sensitive to radiation than cancer cells – absorb less of it. When healthy cells absorb less radiation, mesothelioma patients have fewer side effects. 

At the same time, if cancer cells become more sensitive to radiation, treatment results are likely to be better.

Why Aren’t Cancer Cells More Sensitive to Radiation?

Radiation is a popular cancer treatment. It damages the DNA of cancer cells, making it harder for them to grow and spread. Radiation can help stimulate the cell death process (apoptosis). 

But mesothelioma cells have a way to protect themselves. They already produce Bcl-2 proteins to prevent apoptosis. Their high amounts of these proteins make them less sensitive to radiation-induced apoptosis. 

The goal of the new Scottish study was to find a way to block Bcl-2 proteins to make mesothelioma radiotherapy more effective. 

Getting Around Mesothelioma Radioresistance

Since Bcl-2 proteins make cells less sensitive to radiation, the Glasgow researchers used a Bcl-2-inhibiting drug. They applied the drug (called A1331852) to mesothelioma cells in the lab. A1331852 “mimics” natural proteins that neutralize Bcl-2.  

“A1331852 exhibited cytotoxic and radiosensitizing activities,” reports lead researcher Mark Jackson. Dr. Jackson is with the Institute of Cancer Sciences at the University of Glasgow. 

On its own, A1331852 prompted apoptosis. But when the team added radiation, the response in 3D clusters of mesothelioma cells (called spheroids) was even stronger. “Combination therapy completely eradicated mesothelioma spheroids,” Jackson writes.

The team confirmed that A1331852 reduced the level of Bcl-2 proteins in cell samples from mesothelioma patients. It also made patient-derived mesothelioma cell samples more sensitive to radiation.

“Intrinsic radioresistance can be overcome by small molecule inhibition of this novel therapeutic target,” the team concludes.

If other studies confirm the findings, drugs that block protective proteins could become a routine part of radiation treatment for mesothelioma.

Source:

Jackson, MR, et al, “Mesothelioma cells depend on the anti-apoptotic protein Bcl-xL for survival and are sensitized to ionizing radiation by BH3-mimetics”, November 28, 2019, International Journal of Radiation Oncology, Biology, Physics, Epub ahead of print, https://www.redjournal.org/article/S0360-3016(19)34068-4/pdf