R. Stupp, W. P. Mason, M. J. Van-den-bent, M. Weller, and B. Fisher, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma, N Engl J Med, vol.352, pp.987-96, 2005.

Y. G. Assaraf, A. Brozovic, A. C. Gonçalves, D. Jurkovicova, and A. Lin?, The multi-factorial nature of clinical multidrug resistance in cancer, Drug Resist Updat, vol.46, p.100645, 2019.

J. Yang, A. P. Berx, G. Blanpain, C. Brabletz, and T. , Guidelines and definitions for research on epithelial-mesenchymal transition, Nat Rev Mol Cell Biol, vol.21, pp.341-52, 2020.

P. B. Gupta, I. Pastushenko, A. Skibinski, C. Blanpain, and C. Kuperwasser, Phenotypic Plasticity: driver of cancer initiation, progression, and therapy resistance, Cell Stem Cell, vol.24, pp.65-78, 2019.

A. Marusyk, M. Janiszewska, and K. Polyak, Intratumor heterogeneity: the rosetta stone of therapy resistance, Cancer Cell, vol.37, pp.471-84, 2020.

I. Pastushenko and C. Blanpain, EMT transition states during tumor progression and metastasis, Trends Cell Biol, vol.29, pp.212-238, 2019.

C. Saygin, D. Matei, R. Majeti, O. Reizes, and J. D. Lathia, Targeting cancer stemness in the clinic: from hype to hope, Cell Stem Cell, vol.24, pp.25-40, 2019.

N. Vasan, J. Baselga, and D. M. Hyman, A view on drug resistance in cancer, Nature, vol.575, pp.299-309, 2019.

S. Fulda, Cell death-based treatment of glioblastoma, Cell Death Dis, vol.9, p.121, 2018.

P. Juin, O. Geneste, F. Gautier, S. Depil, and M. Campone, Decoding and unlocking the BCL-2 dependency of cancer cells, Nat Rev Cancer, vol.13, pp.455-65, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-02481124

E. Brocard, K. Oizel, L. Lalier, C. Pecqueur, and F. Paris, Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling, Oncotarget, vol.6, pp.6840-6849, 2015.

S. Valès, G. Bacola, M. Biraud, M. Touvron, and A. Bessard, Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis, EBioMedicine, vol.49, pp.172-88, 2019.

N. Q. Balaban, S. Helaine, K. Lewis, M. Ackermann, and B. Aldridge, Definitions and guidelines for research on antibiotic persistence, Nat Rev Microbiol, vol.17, pp.441-449, 2019.
URL : https://hal.archives-ouvertes.fr/pasteur-02558489

G. D. Guler, C. A. Tindell, R. Pitti, C. Wilson, and K. Nichols, Repression of stress-induced LINE-1 expression protects cancer cell subpopulations from lethal drug exposure, Cancer Cell, vol.32, pp.221-258, 2017.

R. Menon, D. Hammerlindl, H. Torrano, J. Schaider, H. Fujita et al., Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer, Theranostics, vol.10, pp.6261-77, 2020.

F. M. Vallette, C. Olivier, F. Lézot, L. Oliver, and D. Cochonneau, Dormant, quiescent, tolerant and persister cells: four synonyms for the same target in cancer, Biochem Pharmacol, vol.162, pp.169-76, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-01947474

H. Hammerlindl and H. Schaider, Tumor cell-intrinsic phenotypic plasticity facilitates adaptive cellular reprogramming driving acquired drug resistance, J Cell Commun Signal, vol.12, pp.133-174, 2018.

M. Ramirez, S. Rajaram, R. J. Steininger, D. Osipchuk, and M. A. Roth, Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells, Nat Commun, vol.7, p.10690, 2016.

K. Lewis, Persister cells, Annu Rev Microbiol, vol.64, pp.357-72, 2010.

N. Kaldalu and T. Tenson, Slow growth causes bacterial persistence, Sci Signal, vol.12, p.1167, 2019.

S. Y. Lee, Temozolomide resistance in Glioblastoma Multiforme, Genes Dis, vol.3, pp.198-210, 2016.

S. J. Danson and M. R. Middleton, Temozolomide: a novel oral alkylating agent, Expert Rev Anticancer Ther, vol.1, pp.13-22, 2001.

I. Talhaoui, B. T. Matkarimov, T. Tchenio, D. O. Zharkov, and M. K. Saparbaev, Aberrant base excision repair pathway of oxidatively damaged DNA: implications for degenerative diseases, Free Radic Biol Med, vol.107, pp.266-77, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02393543

L. Karayan-tapon, V. Quillien, J. Guilhot, M. Wager, and G. Fromont, Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods, J Neurooncol, vol.97, pp.311-333, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00435222

P. F. Cartron, E. Hervouet, E. Debien, C. Olivier, and D. Pouliquen, Folate supplementation limits the tumourigenesis in rodent models of gliomagenesis, Eur J Cancer, vol.48, pp.2431-2472, 2012.

M. Esteller, J. Garcia-foncillas, E. Andion, S. N. Goodman, and O. F. Hidalgo, Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents, N Engl J Med, vol.343, pp.1350-1354, 2000.

E. Hervouet, E. Debien, L. Campion, J. Charbord, and J. Menanteau, Folate supplementation limits the aggressiveness of glioma via the remethylation of DNA repeats element and genes governing apoptosis and proliferation, Clin Cancer Res, vol.15, pp.3519-3548, 2009.

M. Christmann, G. Nagel, S. Horn, U. Krahn, and D. Wiewrodt, MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma, Int J Cancer, vol.127, pp.2106-2124, 2010.

D. Wiewrodt, G. Nagel, N. Dreimüller, T. Hundsberger, and A. Perneczky, MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome, Int J Cancer, vol.122, pp.1391-1400, 2008.

Y. Zhang, C. Dube, M. Gibert, N. Cruickshanks, and B. Wang, The p53 pathway in glioblastoma, Cancers (Basel), vol.10, p.297, 2018.

A. Belter, J. Barciszewski, and A. M. Barciszewska, Revealing the epigenetic effect of temozolomide on glioblastoma cell lines in therapeutic conditions, PLoS One, vol.15, p.229534, 2020.

E. B. Dinca, K. V. Lu, J. N. Sarkaria, R. O. Pieper, and M. D. Prados, p53 small molecule inhibitor enhances temozolomide cytotoxic activity against intracranial glioblastoma xenografts, Cancer Res, vol.68, pp.10034-10043, 2008.

F. He, W. Borcherds, T. Song, X. Wei, and M. Das, Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding, Proc Natl Acad Sci, vol.116, pp.8859-68, 2019.

M. E. Hegi, A. C. Diserens, T. Gorlia, M. F. Hamou, and N. De-tribolet, MGMT gene silencing and benefit from temozolomide in glioblastoma, N Engl J Med, vol.352, pp.997-1003, 2005.

C. J. O'regan, H. Kearney, A. Beausang, M. A. Farrell, and F. M. Brett, Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol, J Neurooncol, vol.137, pp.233-273, 2018.

X. Chen, M. Zhang, H. Gan, H. Wang, and J. H. Lee, A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma, Nat Commun, vol.9, p.2949, 2018.

C. F. De-souza, T. S. Sabedot, T. M. Malta, L. Stetson, and O. Morozova, A distinct DNA methylation shift in a subset of glioma CpG island methylator phenotypes during tumor recurrence, Cell Rep, vol.23, pp.637-51, 2018.

C. Lu, Y. Wei, X. Wang, Z. Zhang, and J. Yin, DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma, Mol Cancer, vol.19, p.28, 2020.

J. Briand, A. Nadaradjane, G. Bougras-cartron, C. Olivier, and F. M. Vallette, Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation, Clin Epigenetics, vol.11, p.159, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-02480992

B. Banelli, A. Daga, A. Forlani, G. Allemanni, and D. Marubbi, Small molecules targeting histone demethylase genes (KDMs) inhibit growth of temozolomide-resistant glioblastoma cells, Oncotarget, vol.8, pp.34896-910, 2017.

B. B. Liau, C. Sievers, L. K. Donohue, S. M. Gillespie, and W. A. Flavahan, Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance, Cell Stem Cell, vol.20, pp.233-279, 2017.

Z. Wang, W. Jiang, Y. Wang, Y. Guo, and Z. Cong, MGMT promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma, Biomed Rep, vol.3, pp.543-551, 2015.

A. Nadaradjane, J. Briand, G. Bougras-cartron, V. Disdero, and F. M. Vallette, MiR-370-3p is a therapeutic tool in anti-glioblastoma therapy but is not an intratumoral or cell-free circulating biomarker, Mol Ther Nucleic Acids, vol.13, pp.642-50, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01982015

J. Estaquier, F. Vallette, J. L. Vayssiere, and B. Mignotte, The mitochondrial pathways of apoptosis, Adv Exp Med Biol, vol.942, pp.157-83, 2012.

A. Rossin, G. Miloro, and A. O. Hueber, TRAIL and FasL functions in cancer and autoimmune diseases: towards an increasing complexity, Cancers (Basel), vol.11, p.639, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02189531

C. Trejo-solís, N. Serrano-garcia, Á. Escamilla-ramírez, R. A. Castillo-rodríguez, and D. Jimenez-farfan, Autophagic and apoptotic pathways as targets for chemotherapy in glioblastoma, Int J Mol Sci, vol.19, p.3773, 2018.

P. F. Cartron, D. Loussouarn, M. Campone, S. A. Martin, and F. M. Vallette, Prognostic impact of the expression/phosphorylation of the BH3-only proteins of the BCL-2 family in glioblastoma multiforme, Cell Death Dis, vol.3, p.421, 2012.

S. Martin, C. Toquet, L. Oliver, P. F. Cartron, and P. Perrin, Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal, J Neurooncol, vol.52, pp.129-168, 2001.

F. Manero, F. Gautier, T. Gallenne, N. Cauquil, and D. Grée, The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death, Cancer Res, vol.66, pp.2757-64, 2006.

C. Gratas, Q. Séry, M. Rabé, L. Oliver, and F. M. Vallette, Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma, Oncotarget, vol.5, pp.2428-2463, 2014.

J. Chang, Y. Wang, L. Shao, R. M. Laberge, and M. Demaria, Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice, Nat Med, vol.22, pp.78-83, 2016.

R. Yamaguchi and G. Perkins, Finding a Panacea among combination cancer therapies, Cancer Res, vol.72, pp.18-23, 2012.

M. A. Taylor, B. C. Das, and S. K. Ray, Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma, Apoptosis, vol.23, pp.563-75, 2018.

M. Buccarelli, M. Marconi, S. Pacioni, D. Pascalis, I. et al., Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis, Cell Death Dis, vol.9, p.841, 2018.

E. Pawlowska, J. Szczepanska, M. Szatkowska, and J. Blasiak, An interplay between senescence, apoptosis and autophagy in glioblastoma multiforme -role in pathogenesis and therapeutic perspective, Int J Mol Sci, vol.19, p.889, 2018.

I. V. Ulasov, G. Lenz, and M. S. Lesniak, Autophagy in glioma cells: an identity crisis with a clinical perspective, Cancer Lett, vol.428, pp.139-185, 2018.

D. Aasland, L. Götzinger, L. Hauck, N. Berte, and J. Meyer, Temozolomide induces senescence and repression of DNA repair pathways in glioblastoma cells via activation of ATR-CHK1, p21, and NF-?B, Cancer Res, vol.79, pp.99-113, 2019.

H. Y. Jeon, J. K. Kim, S. W. Ham, S. Y. Oh, and J. Kim, Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype, Tumour Biol, vol.37, pp.5857-67, 2016.

M. T. Tomicic and M. Christmann, Targeting anticancer drug-induced senescence in glioblastoma therapy, Oncotarget, vol.9, pp.37466-37473, 2018.

N. Gammoh, J. Fraser, C. Puente, H. M. Syred, and H. Kang, Suppression of autophagy impedes glioblastoma development and induces senescence, Autophagy, vol.12, pp.1431-1440, 2016.

A. C. Tien, J. Li, X. Bao, A. Derogatis, and S. Kim, A phase 0 trial of Ribociclib in recurrent glioblastoma patients incorporating a tumor pharmacodynamic-andpharmacokinetic-guided expansion cohort, Clin Cancer Res, vol.25, pp.5777-86, 2019.

A. Nagy, K. Eder, M. A. Selak, and B. Kalman, Mitochondrial energy metabolism and apoptosis regulation in glioblastoma, Brain Res, vol.1595, pp.127-169, 2015.

K. Oizel, C. Chauvin, L. Oliver, C. Gratas, and F. Geraldo, Efficient mitochondrial glutamine targeting prevails over glioblastoma metabolic plasticity, Clin Cancer Res, vol.23, pp.6292-304, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-01595798

J. H. Lee, J. E. Lee, J. Y. Kahng, S. H. Kim, and J. S. Park, Human glioblastoma arises from subventricular zone cells with low-level driver mutations, Nature, vol.560, pp.243-250, 2018.

Z. Zhu, S. Du, Y. Du, J. Ren, and G. Ying, Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis, J Neurochem, vol.144, pp.93-104, 2018.

E. Singer, J. Judkins, N. Salomonis, L. Matlaf, and P. Soteropoulos, Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma, Cell Death Dis, vol.6, p.1601, 2015.

A. Lo-dico, A. Salvatore, C. Martelli, D. Ronchi, and C. Diceglie, Intracellular redox-balance involvement in temozolomide resistancerelated molecular mechanisms in glioblastoma, Cells, vol.8, p.1315, 2019.

E. D. Michelakis, G. Sutendra, P. Dromparis, L. Webster, and A. Haromy, Metabolic modulation of glioblastoma with dichloroacetate, Sci Transl Med, vol.2, pp.31-34, 2010.

M. Morfouace, L. Lalier, M. Bahut, V. Bonnamain, and P. Naveilhan, Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications, J Biol Chem, vol.287, pp.33664-74, 2012.

M. Morfouace, L. Lalier, L. Oliver, M. Cheray, and C. Pecqueur, Control of glioma cell death and differentiation by PKM2-Oct4 interaction, Cell Death Dis, vol.5, p.1036, 2014.

L. Shen, J. Zhu, F. Chen, W. Lin, and J. Cai, RUNX1-Evi-1 fusion gene inhibited differentiation and apoptosis in myelopoiesis: an in vivo study, BMC Cancer, vol.15, p.970, 2015.

K. Oizel, C. Gratas, A. Nadaradjane, L. Oliver, and F. M. Vallette, D-2-Hydroxyglutarate does not mimic all the IDH mutation effects, in particular the reduced etoposide-triggered apoptosis mediated by an alteration in mitochondrial NADH, Cell Death Dis, vol.6, p.1704, 2015.
URL : https://hal.archives-ouvertes.fr/inserm-01818661

H. Lin, S. Patel, V. S. Affleck, I. Wilson, and D. M. Turnbull, Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells, Neuro Oncol, vol.19, pp.43-54, 2017.

K. Al-nedawi, J. Meehan, V. Micallef, L. Lhotak, and A. May, Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells, Nat Cell Biol, vol.10, pp.619-643, 2008.

C. Corcoran, S. Rani, K. O'brien, O. Neill, A. Prencipe et al., Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes, PLoS One, vol.7, p.50999, 2012.

K. B. Challagundla, P. M. Wise, P. Neviani, H. Chava, and M. Murtadha, Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy, J Natl Cancer Inst, vol.107, p.135, 2015.

L. Mao, J. Li, W. X. Chen, Y. Q. Cai, and D. D. Yu, Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs, Tumour Biol, vol.37, pp.5247-56, 2016.

R. Medikonda, G. Dunn, M. Rahman, P. Fecci, and M. Lim, A review of Glioblastoma immunotherapy, J Neurooncol, 2020.

C. Chauvin, N. Joalland, J. Perroteau, U. Jarry, and L. Lafrance, NKG2D controls natural reactivity of V?9V?2 T lymphocytes against mesenchymal glioblastoma cells, Clin Cancer Res, vol.25, pp.7218-7246, 2019.

S. Sengupta, J. Marrinan, C. Frishman, and P. Sampath, Impact of temozolomide on immune response during malignant glioma chemotherapy, Clin Dev Immunol, vol.2012, p.831090, 2012.

M. Candolfi, K. Yagiz, M. Wibowo, G. E. Ahlzadeh, and M. Puntel, Temozolomide does not impair gene therapy-mediated antitumor immunity in syngeneic brain tumor models, Clin Cancer Res, vol.20, pp.1555-65, 2014.

A. Karachi, F. Dastmalchi, D. A. Mitchell, and M. Rahman, Temozolomide for immunomodulation in the treatment of glioblastoma, Neuro Oncol, vol.20, pp.1566-72, 2018.

H. Noh, Q. Zhao, J. Yan, L. Y. Kong, and K. Gabrusiewicz, Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells, Cancer Lett, vol.433, pp.176-85, 2018.

J. Fleurence, M. Bahri, S. Fougeray, S. Faraj, and S. Vermeulen, Impairing temozolomide resistance driven by glioma stem-like cells with adjuvant immunotherapy targeting O-acetyl GD2 ganglioside, Int J Cancer, vol.146, pp.424-462, 2020.
URL : https://hal.archives-ouvertes.fr/inserm-02168202

A. Karachi, C. Yang, F. Dastmalchi, E. J. Sayour, and J. Huang, Modulation of temozolomide dose differentially affects T-cell response to immune checkpoint inhibition, Neuro Oncol, vol.21, pp.730-771, 2019.

J. Wei, P. Chen, P. Gupta, M. Ott, and D. Zamler, Immune biology of glioma-associated macrophages and microglia: functional and therapeutic implications, Neuro Oncol, vol.22, pp.180-94, 2020.

S. Bao, Q. Wu, R. E. Mclendon, Y. Hao, and Q. Shi, Glioma stem cells promote radioresistance by preferential activation of the DNA damage response, Nature, vol.444, pp.756-60, 2006.

R. C. Gimple, S. Bhargava, D. Dixit, and J. N. Rich, Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer, Genes Dev, vol.33, pp.591-609, 2019.

D. A. Aderetti, V. Hira, R. J. Molenaar, and C. Van-noorden, The hypoxic peri-arteriolar glioma stem cell niche, an integrated concept of five types of niches in human glioblastoma, Biochim Biophys Acta Rev Cancer, vol.1869, pp.346-54, 2018.

R. G. Verhaak, K. A. Hoadley, E. Purdom, V. Wang, and Y. Qi, Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell, vol.17, pp.98-110, 2010.

M. Rabé, S. Dumont, A. Álvarez-arenas, H. Janati, and J. Belmonte-beitia, Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma, Cell Death Dis, vol.11, p.19, 2020.

L. B. Hoang-minh, F. A. Siebzehnrubl, C. Yang, S. Suzuki-hatano, and K. Dajac, Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma, EMBO J, vol.37, p.98772, 2018.

A. Quinones and A. Le, The multifaceted metabolism of glioblastoma, Adv Exp Med Biol, vol.1063, pp.59-72, 2018.

A. Dongre and R. A. Weinberg, New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer, Nat Rev Mol Cell Biol, vol.20, pp.69-84, 2019.

M. Fedele, L. Cerchia, S. Pegoraro, R. Sgarra, and G. Manfioletti, Proneural-mesenchymal transition: phenotypic plasticity to acquire multitherapy resistance in glioblastoma, Int J Mol Sci, vol.20, p.2746, 2019.

M. L. Broekman, S. Maas, E. R. Abels, T. R. Mempel, and A. M. Krichevsky, Multidimensional communication in the microenvirons of glioblastoma, Nat Rev Neurol, vol.14, pp.482-95, 2018.