Belgian scientists have figured out why certain types of cancer become resistant to chemotherapy. By turning off genes that produce proteins involved in chemotherapy resistance, they were able to make resistant cancer cells more sensitive to treatment.
Despite new developments in targeted therapies, chemotherapy remains the mainstay of cancer treatment. However, patients may develop resistance to chemotherapy, causing cancer cells to evade its cancer-killing effects.
A process called epithelial-mesenchymal transition (EMT) has been shown to control cancer tumor initiation, progression, metastasis, and resistance to chemotherapy. EMT causes epithelial cancer cells to lose their ability to adhere to neighboring cells, increasing their mobility and invasiveness. However, the mechanisms by which EMT influences chemoresistance are poorly understood.
Researchers at the Université Libre de Bruxelles conducted experiments on mice genetically engineered to have cutaneous squamous cell carcinoma (SCC), the second most common type of skin cancer. Researchers looked at cancer cells displaying EMT to investigate the response that different cell populations had to chemotherapy.
Mice received standard chemotherapy used to treat humans with metastatic SCC. The researchers found that cancer cells presenting EMT were highly resistant to chemotherapy, and her RHOJ gene was highly expressed in chemotherapy-resistant cells. This gene encodes a small GTP-binding protein, also called RHOJ. GTP-binding proteins transmit signals to the outside of the cell, causing changes inside the cell.
Importantly, the researchers found that suppressing RHOJ expression sensitized cancer cells to chemotherapy. By examining the RHOJ protein, we discovered the mechanism by which RHOJ renders cells resistant to chemotherapy. RHOJ has been found to activate DNA repair pathways in cells after DNA damage is induced by chemotherapy. This allowed cancer cells to self-repair and escape death.
This study provides a deeper understanding of the genetic mechanisms underlying certain types of chemotherapy-resistant cancers, which will have important implications for future therapeutic development.
“Our finding that inhibition of a single gene can sensitize cancer cells to chemotherapy has implications for the development of drugs targeting RHOJ that should reduce resistance to chemotherapy in cancer patients presenting with EMT. It opens up new avenues,” said Cédric Blanpain.Study.
The study was published in a journal Nature.
Source: Free University of Brussels via EurekAlert!
