ESTRO 2024 - Abstract Book

S5417

Radiobiology - Tumour biology

ESTRO 2024

Whereas the expression of BRD2 and BRD3 was not significantly affected by BETi, BRD4 was down-regulated by dBET6 but upregulated by trotabresib in both cell lines. Interestingly, both BETi reduced the expression of MYC.

Conclusion:

In summary, our results demonstrate that BET inhibitors diminish the radioresistant S-phase, decrease the expression of the oncogene MYC and increase the radiosensitivity of radioresistant GBM cells.

These in vitro data indicate that BET inhibition in combination with radiotherapy might provide a promising novel therapeutic approach for patients with GBM.

To prove the translation into clinic, further studies will be performed to validate the radiosensitization in primary patient-derived GBM and to characterize the underlying radiobiological mechanisms.

Keywords: glioblastoma, radiosensitization, BET inhibition

References:

[1] Duan W, Yu M, Chen J. BRD4: New hope in the battle against glioblastoma. Pharmacological research. 2023;191:106767.

[2] Vieito M, Simonelli M, de Vos F, Moreno V, Geurts M, Lorenzi E, et al. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma. Neurooncol Adv. 2022;4:vdac146. [3] Moreno V, Sepulveda JM, Vieito M, Hernandez-Guerrero T, Doger B, Saavedra O, et al. Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2020;31:780-8. [4] Xu L, Chen Y, Mayakonda A, Koh L, Chong YK, Buckley DL, et al. Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma. Proceedings of the National Academy of Sciences of the United States of America. 2018;115:E5086-E95.

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Digital Poster

An in vitro and in silico study of sex-linked genes and treatment response in lung cancer

Amy Kinsella 1 , Adriele Prina-Mello 2 , Laure H Marignol 1

1 Trinity St. James’s Cancer Institute, Radiobiology and Molecular oncology Research group, Applied Radiation Therapy Trinity, Trinity College Dublin, Radiation Therapy, Dublin, Ireland. 2 Laboratory for Biological Characterization of