Chemotherapy May Act as a Double-Edged Sword With Mesothelioma Cells

Nearly any patient diagnosed with pleural mesothelioma, an asbestos-caused cancer, will be treated with chemotherapy at some point. The chemotherapy drugs for mesothelioma work by attacking cancer cells with its deadly chemicals, ultimately killing the cancer and halting the cancer from growing. Now, researchers say one mesothelioma chemotherapy drug, sometimes used in mesothelioma treatment, has been shown to actually spur cancer growth.

In a recent study from The Ohio State University, (https://news.osu.edu/news/2017/08/07/chemo-paradox/) researchers found that in a breast cancer mouse model treated with paclitaxel, the drug “sets off a variety of molecular-level changes” that has cancer cells escape the tumor while at the same time making the lung more inviting to the cells. This reaction counteracts the benefits of the chemotherapy contributing to chemo-resistance and metastasis.

“That chemotherapy can paradoxically promote cancer progression is an emerging revelation in cancer research,” said Tsonwin Hai, the study’s senior author and a professor of biological chemistry and pharmacology. “However, a molecular-level understanding of this devastating effect is not clear.”

When Hai sought to better understand how the lung environment enticed the cancer cells, she discovered that the ATF3 gene that is usually “turned on by stress,” was expressed in higher levels in chemotherapy patients.

Using an analogy to gardening, with the cancer cells being the seeds and the lung being the soil, Hai said the gene both distributes the seeds and fertilizes the soil at the same time. This process, she says, is very active with the cells being “beckoned” to freely travel from the tumor to other organs.

For patients diagnosed with lung cancer or mesothelioma, chemotherapy is the most commonly prescribed treatment for managing symptoms and slowing the growth of the disease. But both cancers have shown to become chemo-resistant, eventually rendering the treatments ineffective.

According to the National Cancer Society, metastasis is the cause of 90 percent of all cancer deaths. Halting tumor growth and preventing metastasis in cancers, especially mesothelioma, a highly aggressive asbestos-caused cancer, is critical for increasing survival in patients.

The researchers concluded: “Because chemotherapy is an important treatment for cancer patients, dampening the effect of ATF3 may help improve the efficacy of chemotherapy.”

Hai plans on continuing this research to determine the impact of these findings on humans, although the data suggests it is relevant to human cancer, and to find ways to combat the metastasis with chemotherapy before it becomes an issue.

“Therefore, at this point, we are not suggesting oncologists to change their clinical practices but would suggest that it is prudent to keep our mind open, realizing that chemotherapy can be a double-edged sword,” said Hai.

Paclitaxel was approved by the U.S. Food and Drug Administration in 2012 for use in combination with carboplatin for the initial treatment of patients with locally advanced or metastatic non-small cell lung cancer. Pleural mesothelioma patients often follow the same treatment protocol as lung cancer patients.

See the full study in the Aug. 7 issue of Proceedings of the National Academy of Sciences. http://www.pnas.org/content/114/34/E7159.abstract?sid=2f9af601-0fd1-468a-af2a-e0c17801b88c

Read about out how researchers are working to improve symptoms of chemotherapy induced peripheral neuropathy, and to find out more about other chemotherapy side effects.