Tumor Microenvironment, Hypoxia, and Stem Cell-Related Radiation Resistance

Sottili, Mariangela; Gerini, Chiara; Desideri, Isacco; Loi, Mauro; Livi, Lorenzo; Mangoni, Monica

doi:10.1007/978-3-319-28305-0_12

Cited by 1 publication

(1 citation statement)

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“…Based on this evidence, a large group of molecularly targeted agents have been designed, but none of them seem to overcome tumor radioresistance [29]. Previous studies support an involvement of the SRC-family protein kinases in the irradiation induction of radioresistance mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line

Cammarata

Torrisi

Forte

et al. 2019

IJMS

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Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments.

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Section: Introductionmentioning

confidence: 99%