Response to Chemotherapy in Mesothelioma Patients: Could This Protein Predict It?

There is new evidence that a protein called Activin A could help predict response to chemotherapy in patients with malignant pleural mesothelioma. It may also make it easier for doctors to distinguish mesothelioma from benign lung tumors.

Activin A influences many cellular processes. Among other things, it plays a role in cell proliferation, immune response, metabolism, and natural cell death. 

FInnish researchers say mesothelioma patients with higher levels of Activin A in their blood are more likely to suffer from cachexia. Cachexia is weakness and wasting of the body due to chronic illness. High expressors of Activin A are also less likely to have a good response to chemotherapy. 

Activin A and Mesothelioma

Activin A is a member of the transforming growth factor beta (TGF-β) family of proteins. Many types of cells produce Activin A, but animal studies show that it tends to be especially high in malignant mesothelioma patients. 

Activin A may influence these patients’ response to chemotherapy and how well their bodies cope with the cancer. 

Researchers at the University of Helsinki took serum samples from 21 patients with pleural mesothelioma, 59 patients with non-small-cell lung cancer, and 22 patients with benign lung lesions. 

Mesothelioma patients had higher levels of Activin A than other study subjects. The higher the Activin A level, the bigger their mesothelioma tumor was likely to be. Patients with the highest levels of Activin A also had the smallest change in tumor size in response to chemotherapy. 

The reverse was also true: “Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease,” write the researchers. 

Why Predict Response to Chemotherapy?

Pleural mesothelioma is a highly aggressive cancer. By the time a patient receives a diagnosis, he or she may have just months to live. It is critical for doctors to find the best treatment fast. Chemotherapy is the primary treatment for mesothelioma but it does not always work. 

If doctors had a tool that could accurately predict a patient’s response to chemotherapy, it could save precious treatment time. For instance, if tests show that chemotherapy with Alimta is unlikely to help a particular mesothelioma patient, doctors could start trying other treatments earlier.

If a patient’s response to chemotherapy is not what doctors were hoping for, it could be helpful to know why. An Activin A test might have the answer. 

But the ability to predict response to chemotherapy is not the only potential value of Activin A. The Finnish study showed Activin A was lower in people with lung cancer than it was in people with mesothelioma. And in people with benign lung tumors, it was much lower. This could make it a useful diagnostic tool.

“Activin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors,” the researchers conclude. It can be tricky to make this distinction from imaging studies alone. 

Source:

Paajanen, J, et al, “Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy”, October 25, 2019, Clinical Lung Cancer, Epub ahead of print, https://www.clinical-lung-cancer.com/article/S1525-7304(19)30287-6/fulltext