Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.
Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318:2306–16.
Qazi MA, Vora P, Venugopal C, Sidhu SS, Moffat J, Swanton C, et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol : J Eur Soc Med Oncol. 2017;28:1448–56.
Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, et al. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci USA. 2012;109:3041–6.
Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev. 2015;29:1203–17.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.
Balbous A, Cortes U, Guilloteau K, Rivet P, Pinel B, Duchesne M, et al. A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells. BMC Cancer. 2016;16:604.
Carruthers R, Ahmed SU, Strathdee K, Gomez-Roman N, Amoah-Buahin E, Watts C, et al. Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase. Mol Oncol. 2015;9:192–203.
Ahmed SU, Carruthers R, Gilmour L, Yildirim S, Watts C, Chalmers AJ. Selective inhibition of parallel DNA damage response pathways optimizes radiosensitization of glioblastoma stem-like cells. Cancer Res. 2015;75:4416–28.
Venere M, Hamerlik P, Wu Q, Rasmussen RD, Song LA, Vasanji A, et al. Therapeutic targeting of constitutive PARP activation compromises stem cell phenotype and survival of glioblastoma-initiating cells. Cell Death Differ. 2014;21:258–69.
Yan F, Alinari L, Lustberg ME, Martin LK, Cordero-Nieves HM, Banasavadi-Siddegowda Y, et al. Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma. Cancer Res. 2014;74:1752–65.
Han X, Li R, Zhang W, Yang X, Wheeler CG, Friedman GK, et al. Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro. J Neurooncol. 2014;118:61–72.
Banasavadi-Siddegowda YK, Russell L, Frair E, Karkhanis VA, Relation T, Yoo JY, et al. PRMT5-PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells. Oncogene. 2017;36:263–74.
Banasavadi-Siddegowda YK, Welker AM, An M, Yang X, Zhou W, Shi G, et al. PRMT5 as a druggable target for glioblastoma therapy. Neuro Oncol. 2018;20:753–63.
Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, et al. PRMT5 inhibition disrupts splicing and stemness in glioblastoma. Nat Commun. 2021;12:979.
Briggs KJ, Cottrell KM, Tonini MR, Tsai A, Zhang M, Whittington DA, et al. TNG908 is a brain-penetrant, MTA-cooperative PRMT5 inhibitor developed for the treatment of MTAP-deleted cancers. Transl Oncol. 2025;52:102264.
Clarke TL, Sanchez-Bailon MP, Chiang K, Reynolds JJ, Herrero-Ruiz J, Bandeiras TM, et al. PRMT5-dependent methylation of the TIP60 coactivator RUVBL1 is a key regulator of homologous recombination. Mol Cell. 2017;65:900–16 e7.
Wang YJ, Cao JB, Yang J, Liu T, Yu HL, He ZX, et al. PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells. Cell Mol Life Sci. 2024;81:123.
Hamard PJ, Santiago GE, Liu F, Karl DL, Martinez C, Man N, et al. PRMT5 regulates DNA repair by controlling the alternative splicing of histone-modifying enzymes. Cell Rep. 2018;24:2643–57.
Owens JL, Beketova E, Liu S, Tinsley SL, Asberry AM, Deng X, et al. PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA double-strand break repair genes. iScience. 2020;23:100750.
Hwang JW, Kim SN, Myung N, Song D, Han G, Bae GU, et al. PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation. Commun Biol. 2020;3:428.
Ortiz R, Perazzoli G, Cabeza L, Jimenez-Luna C, Luque R, Prados J, et al. Temozolomide: an updated overview of resistance mechanisms, nanotechnology advances and clinical applications. Curr Neuropharmacol. 2021;19:513–37.
Jezierzanski M, Nafalska N, Stopyra M, Furgol T, Miciak M, Kabut J, et al. Temozolomide (TMZ) in the treatment of glioblastoma multiforme-a literature review and clinical outcomes. Curr Oncol. 2024;31:3994–4002.
Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488:522–6.
Orzan F, De Bacco F, Crisafulli G, Pellegatta S, Mussolin B, Siravegna G, et al. Genetic evolution of glioblastoma stem-like cells from primary to recurrent tumor. Stem Cells. 2017;35:2218–28.
Li H, Chen L, Li JJ, Zhou Q, Huang A, Liu WW, et al. miR-519a enhances chemosensitivity and promotes autophagy in glioblastoma by targeting STAT3/Bcl2 signaling pathway. J Hematol Oncol. 2018;11:70.
Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT, Brock C. Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev. 1997;23:35–61.
Hirose Y, Berger MS, Pieper RO. Abrogation of the Chk1-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Cancer Res. 2001;61:5843–9.
Chen CC, Taniguchi T, D’Andrea A. The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents. J Mol Med (Berl). 2007;85:497–509.
Du C, Li SW, Singh SX, Roso K, Sun MA, Pirozzi CJ, et al. Epigenetic regulation of Fanconi anemia genes implicates PRMT5 blockage as a strategy for tumor chemosensitization. Mol Cancer Res. 2021;19:2046–56.
Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, et al. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol. 2010;12:116–21.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.
Short SC, Giampieri S, Worku M, Alcaide-German M, Sioftanos G, Bourne S, et al. Rad51 inhibition is an effective means of targeting DNA repair in glioma models and CD133+ tumor-derived cells. Neuro Oncol. 2011;13:487–99.
Quiros S, Roos WP, Kaina B. Rad51 and BRCA2-New molecular targets for sensitizing glioma cells to alkylating anticancer drugs. PLoS ONE. 2011;6:e27183.
King HO, Brend T, Payne HL, Wright A, Ward TA, Patel K, et al. RAD51 is a selective DNA repair target to radiosensitize glioma stem cells. Stem Cell Rep. 2017;8:125–39.
Gillespie MS, Chiang K, Regan-Mochrie GL, Choi SY, Ward CM, Sahay D, et al. PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells. Oncogene. 2025;44:862–76.
Alejo S, Palacios BE, Venkata PP, He Y, Li W, Johnson JD, et al. Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma. Neuro Oncol. 2023;25:1249–61.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34:267–73.
Otani Y, Sur HP, Rachaiah G, Namagiri S, Chowdhury A, Lewis CT, et al. Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma. Neuro Oncol. 2021;23:1481–93.

