A recently published article in Experimental Biology and Medicine (Volume 247, Issue 5, March, 2022) identifies a new biomarker for resistance to radiotherapy. The study, led by Dr. Chunling Jiang, in the Department of Radiation Oncology at Jiangxi Cancer Hospital (China), reports that Mut L homolog-1, which participates in DNA mismatch repair, modulates resistance to radiotherapy. 

Ionizing radiation is a mainline therapy in the treatment of many cancers. Ionizing radiation produces many types of DNA damage that kill the cancer cells. However, cancer cells can survive if their DNA repair pathways are able to correct the damage. Mut L homologue-1 (MLH1) is a key DNA mismatch repair protein. However, its role in the cellular response to ionizing radiation has not been elucidated. 

In this study, Dr. Jiang and colleagues examined the role of Mut L homologue-1 (MLH1) in the survival of colorectal cancer cells exposed to ionizing radiation. Cells that expressed MLH1 exhibited increased survival, decreased levels of DNA damage markers and increases in protein kinase A catalytic subunit (PRKAC), which is a common anti-cancer drug target. Furthermore, silencing PRKAC in cells expressing MLH1 increased radiosensitivity. This is the first study to suggest that PRKAC may be a potential biomarker and therapeutic target for radiosensitization. Dr. Jiang said, "Although some radiosensitive tumours can be treated reliably by radiotherapy, most tumours have low sensitivity to radiotherapy. This may be of interest in the development of molecular labelling for assessing radiosensitivity and a new strategy for radiosensitization."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, "Dr. Jiang and colleagues have provided clear evidence that protein Kinase A (PKA) plays an important role in MLH1- mediated radiosensitivity in human colorectal cancer HCT116 cells. This provides the impetus for future studies to uncover how Mut L homologue-1 ( MLH1) affects protein and phosphorylation levels of the PKA catalytic subunit (PRKAC) and what downstream pathways impact PRKAC related radiosensitization."

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