Cancer: Discovery of a protein controlling resistance to chemotherapy
Researchers from the Université libre de Bruxelles (ULB) have discovered a protein, RHOJ, which controls cancer cells' resistance to chemotherapy.
Despite the recent development of new targeted therapies, chemotherapies remain the most frequently used treatment to treat patients suffering from advanced cancers. Chemotherapy resistance is one of the main causes of treatment failure and death in cancer patients.
It has been suggested that the epithelial-mesenchymal transition (EMT), a process by which epithelial cells detach from their neighbouring cells and acquire invasive properties, plays a role in the acquisition of resistance to anti-cancer therapy. However, the mechanism by which cancer cells presenting EMT resist to anti-cancer therapy is currently unknown.
In a study published in Nature, researchers led by Professor Cédric Blanpain at ULB discovered that a protein named RHOJ allows cancer cells presenting EMT to resist anti-cancer treatments by stimulating the repair of DNA damage caused by the chemotherapy.
ULB's researchers found that RHOJ expression was particularly high in chemotherapy-resistant cells after which they showed that by silencing RHOJ, cancer cells became sensitive to chemotherapy.
Maud Debaugnies and her colleagues then studied why RHOJ makes cancer cells resistant to chemotherapy. Chemotherapy induces DNA damage in cancer cells which activates the death of these cells. They discovered that RHOJ can activate the DNA damage repair pathway induced by chemotherapy, allowing cancer cells to repair the DNA lesions and escape cell death.
Understanding these mechanisms that make cancer cells resistant to chemotherapy should open new avenues for the development of new, more effective therapeutic strategies for fighting cancer.