Mechanism of Chemotherapeutic Resistance Elucidated

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(ChemotherapyAdvisor) – Cells that neighbor tumors produce proteins that contribute to chemotherapeutic resistance, according to a team of US-based researchers. This conclusion is based on a study entitled “Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B,” which was published online in Nature Medicine on August 5.

Curing advanced cancer is difficult mainly due to resistance to chemotherapeutic agents. Because chemotherapeutic agents not only kill cancer cells, but also healthy cells, they have to be administered in small doses over time in cycles. In between the cycles of treatment, healthy cells are allowed time to recover. During this treatment break, however, cancer cells that have survived the previous cycles of chemotherapy develop resistance to the chemotherapeutic agents, making them nearly impossible to kill.

The mechanisms of chemotherapeutic resistance are not well understood. However, previous lines of evidence demonstrate that components of the tumor microenvironment, that is, the identity of cell types (and molecules they produce) neighboring the tumor, profoundly influence tumor behavior, including resistance to chemotherapy. In the current study, the investigators aimed to further deduce the role of the tumor microenvironment in the development of chemotherapeutic resistance. To meet this aim, they performed a large gene expression analysis in cancer cells that examined the changes in gene expression that occur in response to chemotherapeutics.

From their gene expression analysis, the investigators identified a number of proteins produced in the tumor microenvironment. It was determined that one of these proteins, known as WNT16B, is produced by the tumor microenvironment in response to DNA damage induced by chemotherapeutic agents. “The expression of WNT16B in the prostate tumor microenvironment attenuated the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression,” the investigators wrote.

The investigators concluded that, based on the results of the study, neighboring cells found in the tissue microenvironment produce proteins that cause tumors to become resistant to chemotherapeutic agents.

Abstract

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