Study identifies new gene which can increase chemotherapeutic response in medulloblastomas
Developing a new therapeutic strategy targeting SLFN11
An international team led by the Department of Neurosurgery, Niigata University, has identified a new gene called Schlafen11 (SLFN11) whose expression is tightly correlated with response to chemotherapy in medulloblastomas, a highly malignant brain tumor affecting pediatric, adolescent, and young adult populations. The team led by Dr. Manabu Natsumeda, first noticed that SLFN11 is highly expressed in almost all cases of WNT-activated medulloblastomas, which is the molecular subgroup with the best prognosis. Further studies using medulloblastoma cell lines showed that genetically manipulating SLFN11 led to drastic changes in response to cisplatin, a key drug for treating this deadly tumor. "Some cases of medulloblastomas respond better to treatment than others, but we did not why. We can now better anticipate which cases will respond to chemotherapy. We even found that by using a different drug called HDAC inhibitor, we can increase SLFN11 levels in tumors and make them more responsive to cisplatin." explains Dr. Natsumeda.
"Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin."
Nakata S, Murai J, Okada M, Takahashi H, Findlay TH, Malebranche K, Parthasarathy A, Miyashita S, Gabdulkhaev R, Benkimoun I, Druillennec S, Chabi S, Hawkins E, Miyahara H, Tateishi K, Yamashita S, Yamada S, Saito T, On J, Watanabe J, Tsukamoto Y, Yoshimura J, Oishi M, Nakano T, Imamura M, Imai C, Yamamoto T, Takeshima H, Sasaki AT, Rodriguez FJ, Nobusawa S, Varlet P, Pouponnot C, Osuka S, Pommier Y, Kakita A, Fujii Y, Raabe EH, Eberhart CG, Natsumeda M.
(Neuro Oncol. 2022 Oct 23;noac243. doi: 10.1093/neuonc/noac243. Online ahead of print.)