On September 22, 2022, the research work entitled “METTL16 antagonizes MRE11-mediated DNA end resection and confers synthetic lethality to PARP inhibition in pancreatic ductal adenocarcinoma” was published in Nature Cancer, and posted on journal cover. This work was conducted by Professor TAO Kaixiong’s team together with Mayo Clinic. The Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is the first affiliation of the paper, with Professor TAO Kaixiong being the co-corresponding author, and Dr. ZENG Xiangyu being the first author. The research provides a new direction for the treatment of pancreatic ductal adenocarcinoma (PDAC).
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with fewer than 10% of patients surviving 5 years. Gemcitabine is the most widely used single-agent chemotherapeutic treatment for PDAC, whereas its effect remains limited. It is a potential strategy for the treatment of PDAC to explore the combination of other targeted drugs with gemcitabine.
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) are the first clinically approved drugs designed to exploit synthetic lethality. PARPis are now a Food and Drug Administration (FDA)-approved standard treatment option as maintenance therapy for patients with metastatic PDAC who harbor pathogenic germline BRCA1/2 mutations. However, only about 10% of patients with PDAC harbor pathogenic mutations of these homologous recombination (HR) genes, leaving most patients missing out on the encouraging treatment strategy. PARPis also show promising activity in more common cancers that share defective HR. Therefore, identifying HR defect markers in PDAC could expand the clinical application of PARPis in PDAC, and benefit more patients.
In this regard, Professor TAO Kaixiong's team of Union Hospital, together with Mayo Clinic, revealed the role of RNA and RNA methyltransferase METTL16 in DNA damage repair, which represents a new regulatory mode of DNA end resection. More importantly, the study demonstrates that a combination of PARPis with gemcitabine could be an effective treatment strategy for PDAC with elevated METTL16 expression.
Source: https://www.whuh.com/info/1021/12706.htm
Edited by: International Exchange Office
