Chemotherapy Resistance in Mesothelioma Patients: New Insights

Canadian cancer researchers have discovered what may be a key cause of chemotherapy resistance in mesothelioma and other types of cancer. The news could lead to more effective ways of treating malignant mesothelioma. 

Chemotherapy resistance is a major problem for mesothelioma patients. The FDA has approved two different drug therapies for mesothelioma. But neither approach seems to hold asbestos cancer at bay long term. 

Scientists at Princess Margaret Cancer Centre in Toronto say it may be because cancer cells “hibernate” to escape attack. If doctors can understand this cancer cell defense mechanism, they might be able to undermine it. 

The Problem of Chemotherapy Resistance

Malignant mesothelioma is the most serious of several illnesses caused by exposure to asbestos. Asbestos fibers work their way deep into the tissue. Over time, the inflammation they cause can alter the DNA and trigger cancer. 

There is no cure for mesothelioma. Since 2004, the primary first-line treatment for mesothelioma has been chemotherapy with Alimta. Last year, the FDA approved two additional drugs. 

But chemotherapy resistance is common with mesothelioma. The treatment may appear to be working at first. But just a few months after chemotherapy stops, mesothelioma starts growing again. This happens with other types of cancer, too. Now, Canadian doctors think they may know why. 

Mesothelioma Cells May “Hibernate” to Protect Themselves

The new research was done on colorectal cancer cells. It shows that their chemotherapy resistance comes from their ability to “hibernate” when attacked by chemotherapy. The cells “wait it out” in this slowed down mode until the threat passes. Researchers called this mode the drug-tolerant persister (DTP) phase.

“All cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs,” writes the research team led by Dr. Catherine O’Brien.

The DTP idea could explain why mesothelioma cells display strong chemotherapy resistance. The DTP state is similar to diapause. This is when embryos of some animals grow slower if the environmental conditions are not ideal for their birth. 

“We need to target cancer cells while they are in this slow-cycling, vulnerable state before they acquire the genetic mutations that drive drug-resistance,” says Dr. O’Brien.

When cancer cells are in the DTP state, they do not grow or need much nutrition. Instead, they consume their own proteins and other cell parts in a process called autophagy. When the scientists interrupted autophagy, they also interrupted chemotherapy resistance.

This suggests that mesothelioma treatment might be more effective if delivered along with a drug that interferes with autophagy. The next step is to validate the research in a larger study. 

More than 2,500 Americans receive a mesothelioma diagnosis each year. Most of them have worked in industries that used asbestos. 

Sources:

Rehman, S, et al, “Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy”, January 7, 2021, Cell, Volume 184, Issue 1, ppp. 226-242, https://www.cell.com/cell/fulltext/S0092-8674(20)31535-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS009286742031535X%3Fshowall%3Dtrue

Ratner, Paul, “Cancer cells hibernate to survive chemotherapy, finds study”, January 12, 2021, Big Think website, https://bigthink.com/surprising-science/cancer-cells-hibernate-chemotherapy?rebelltitem=1#rebelltitem1