Sensitizer Could Improve Radiotherapy for Pleural Mesothelioma

A chemical compound that sensitizes cancer cells to radiation could help improve radiotherapy for pleural mesothelioma.

Radiotherapy uses ionizing radiation to scramble the DNA of cancer cells. This makes it harder for cells to replicate and form new tumors. 

But mesothelioma cells and other hard-to-treat cancers have ways of protecting themselves against radiation-induced DNA damage. The possibility of damaging healthy cells is another limiting factor in radiotherapy for pleural mesothelioma. 

Now, a Japanese study of mice shows a new compound called SQAP can enhance the damage to cancer cells from radiation. The researchers are hopeful it could help keep mesothelioma tumors in check.

The Challenge of Radiotherapy for Pleural Mesothelioma

Malignant pleural mesothelioma is difficult to treat. This aggressive membrane cancer is resistant to most standard cancer therapies, including radiotherapy. Many people diagnosed with mesothelioma die within a few months to a year. 

The flat size and irregular shape of mesothelioma tumors makes them especially hard to irradiate. Radiation has to be highly targeted to keep the surrounding organs from absorbing too much of it. If this happens, patients can develop serious side effects. 

Right now, doctors mostly use radiotherapy for pleural mesothelioma to shrink tumors before surgery. It is sometimes used after other treatments to keep tumors from coming back. But if tumors could be made more sensitive, radiotherapy might become a more effective weapon against mesothelioma.

How SQAP May Help Fight Mesothelioma

The new Japanese study focused on a compound called α-sulfoquinovosyl-acylpropanediol (SQAP). It is a radiosensitizer. Previous studies show it enhances the effect of γ-radiation in human lung and prostate cancer cell lines.

Tests of SQAP and radiotherapy for pleural mesothelioma took place at Nagasaki University Graduate School of Biomedical Sciences. Researchers used two kinds of human mesothelioma cells. They injected the cells into the thoracic cavities and just under the skin on the backs of mice. 

“Then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy,” explains lead researcher Eiko Inamasu. The cells treated with SQAP and radiotherapy for pleural mesothelioma showed several signs of improvement. 

“Immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group,” writes Dr. Inamasu. 

The treatment also appeared to change conditions in the tumor to bring in more oxygen. This may also make tumors more susceptible to radiotherapy for pleural mesothelioma.

Source:

Inamasu, E et al, “Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models”, November 5, 2021, Journal of Radiation Research, https://academic.oup.com/jrr/advance-article/doi/10.1093/jrr/rrab090/6414417