How does prior radiation make gliomas grow faster?
Although brain radiation temporarily causes tumor cells to stop growing, radiation also changes the brain microenvironment, causing even normal brain cells to become senescent. Unfortunately, gliomas invariably eventually recur to become aggressive treatment-resistant and rapidly fatal brain cancers. We have found that placing human tumor cells within a radiated brain microenvironment encourages aggressive behavior. With our collaborators, including Dr. Burma, we have found that eliminating senescent cells may help decrease tumor aggressiveness after brain tumor therapy.
Gupta1K, Vuckovic I, Zhang S, Xiong Y, Carlson BL, Jacobs J, Olson I, Petterson X, Macura SI, Sarkaria J, Burns TC. Radiation induced metabolic alterations associate with tumor aggressiveness and poor outcome in glioblastoma. Frontiers in Oncology. 2020; doi:10.3389/fonc.2020.00535.
Zhang J, Olson IE, Carlstrom LP, Rahman M, Rajani K, Gupta K, Liu L, Tang Z, Sananikone EF, Dong A, Warrington AE, Rodriguez M, Chen J, Schroeder MA, Ikram S, Sarkaria JN, Burma S, Burns TC. Impact of the radiated brain microenvironment on a panel of human patient-derived xenografts. bioRxiv; preprint. 2020; doi:10.1101/2020.06.03.132365.
Fletcher-Sananikone E, Kanji S, Tomimatsu N, Macedo D, Cristofaro LF, Kollipara RK, Saha D, Floyd JR, Sung P, Hromas R, Burns TC, Kittler R, Habib AA, Mukherjee B, Burma S. Elimination of radiation-induced senescence in the brain tumor microenvironment attenuates glioblastoma recurrence. Cancer Research. 2021; doi:10.1158/0008-5472.CAN-21-0752.