BCRB 2018

19/09/2018

Contextual lethality

• High specificity • Low toxicity (different from RT) • Interaction with RT • Radiosensitivity • Hypoxia • Proliferation • Therapeutic index • Target driven • Synthetic lethality • Contextual lethality • Immune modulation

Hanahan & Weinberg Cell 2011

Immune modulation

Herrera FG et al CA Cancer J Clin 2017

• Clinical efficacy of RT • Traditionally: local effect, through direct tumor cell death (DNA damage) • More recently: systemic effects on “out-of-field” tumor deposits = abscopal effect, mediated by immune mechanisms

• RT induces ‘in situ’ vaccination • RT reprograms the tumor micro-environment

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