Research explores how cancer cells develop resistance to chemotherapy

Cancer cells sometimes develop resistance to cytotoxic drugs used in chemotherapy. It is therefore important to understand why the treatment does not work and why it may even defeat its own purpose.

We haven’t really understood how this resistance to chemotherapy develops let alone how the cancer microenvironment can affect the process. “

Kaisa Lehti, Professor, Department of Biomedical Laboratory Sciences, Norwegian University of Science and Technology (NTNU)

Lehti led the work to better understand how cancerous tissue develops resistance to a particular form of chemotherapy. The University of Helsinki, the Karolinska Institutet and the NTNU collaborated in the research. The results have now been published in the much respected Nature Communication newspaper.

Standard treatment may fail

Ovarian cancer affects around 500 Norwegian women each year. If cancer is caught early, almost all patients survive the first five years. But if it is discovered later, the chances of survival are much worse. Finding an effective treatment is therefore very important.

One of the standard treatments for ovarian cancer is called platinum-based chemotherapy. Cytotoxins are so named because they contain platinum compounds. They are often effective in the treatment of various cancers.

Unfortunately, cancer cells often develop resistance to this particular platinum-based chemotherapy treatment. The solution lies in how the cytotoxin itself can modify cancer cells and their environment.

Cytotoxin changes cancer cells and the environment

Lehti summarizes the process. “Cytotoxin can change the way cancer cells send and perceive signals and can alter the microenvironment around cells.”

This change allows cancer cells to resist cytotoxin damage – and thus can survive the chemotherapy attack. Researchers found this key to the puzzle in a layer of tissue that often surrounds cancer cells.

“A fibrous network of proteins, known as the extracellular matrix or ECM, surrounds cancer cells, especially the more aggressive ones,” explains Lehti.

Builds resistance

Fibrotic tissue is formed when the body tries to repair an injury. Fibrous tissue, along with the ECM network around cancer cells, is primarily produced by normal connective tissue cells. But cancer cells and connective tissue cells in the network can themselves damage this tissue.

“Previously, we didn’t know how the communication between cancer cells and the extracellular matrix is ​​affected by, or even influences itself, the development of cancer and its response to chemotherapy,” explains Lehti.

But we know more about it now. Chemical and mechanical signals in the surrounding ECM tissue are already known to help cancer develop its ability to spread and resist treatment.

“Certain ECM signals can critically alter the resistance of cancer cells to platinum-based cytotoxic drugs,” explains Prof. Kaisa Lehti.

The cytotoxin can thus help modify both the microenvironment around cancer cells and the ability of cancer cells to receive and sense signals in the environment that help them resist the cytotoxin. This can eventually prevent the cytotoxin from working.

The increased knowledge of these mechanisms is useful when choosing treatments for people with cancer.