ESTRO 2024 - Abstract Book

S5399

Radiobiology - Tumour biology

ESTRO 2024

pathway resulting in enhanced cell survival and migration/invasion in other cancers. Here, we found that TAGLN2 regulated the PI3K/AKT oncogenic pathway in GBM cell lines and KD of TAGLN2 reduced activated AKT (pAKT) levels resulting in downregulation of this pathway. Subsequently, we also found that TAGLN2 activated this pathway by binding to and inhibiting PTEN. Using in silico virtual screening and a series of in vitro assays, a number of SMIs of TAGLN2 were identified that were able to permeate blood brain barrier (BBB). These inhibitors showed high-affinity binding to TAGLN2 and reduced the level of Transgelin-2 protein in primary GBM lines in a dose- and time-dependent fashion. Genetic KD of TAGLN2 as well as SMIs-mediated inhibition of TAGLN2 increased the sensitivity of GBM cells to both temozolomide and radiation as assessed by a series of in vitro assays. Finally, In vivo data using an orthotopic xenograft mouse model showed marked reduction of tumor growth following genetic KD of TAGLN2. In vivo xenograft mouse model experiments are underway to test the efficacy and toxicity of these select SMIs. Further, the systemic toxicity of these compounds will be tested in immunocompetent mice.

Conclusion:

Our data suggest that TAGLN2 contributes to cell proliferation, invasion and plays an important role in chemo radiation treatment resistance in GBM. TAGLN2 may confer treatment resistance through upregulation of the PI3K/AKT oncogenic pathway by inhibiting PTEN functions. Thus, TAGLN2 may overcome therapeutic resistance in GBM.

Keywords: TAGLN2, GBM, PTEN

2094

Digital Poster

Toxicity and risk of induced second cancer in the treatment of prostate cancer using VMAT and 3D-CRT

Cheikh Tayeb 1 , Assya Boughalia 2

1 Central army hospital, Radiation oncology, Algiers, Algeria. 2 Nuclear Research Center of Algiers, Atomic and Radiologic Physics, Algiers, Algeria

Purpose/Objective:

Induced secondary cancers and toxicities after radiotherapy is an undesired outcome of the therapy that can be observed in long ‐ term cancer survivors. The factors that impact secondary cancer risk which can be analyzed from a radiobiological perspective: age at irradiation, type of irradiated tissue, irradiated volume, treatment modality, previous irradiation/radiological investigations. The aim of this study was to assess the induced secondary cancer and toxicities using Excess absolute risk (EAR) based on the concept of organ equivalent dose (OED) developed by Uwe Schneider and equivalent uniform dose (EUD) from Niemerko respectively in case of conformal therapy compared to Tomotherapy.

Material/Methods: