Abstract
The efficacy of radiotherapy critically depends on the activation of intrinsic cell death programs in cancer cells. This implies that evasion of cell death, a hallmark of human cancers, can contribute to radioresistance. Therefore, novel strategies to reactivate cell death programs in cancer cells are required in order to overcome resistance to radiotherapy. Since Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in multiple cancers and block cell death induction at a central point, therapeutic targeting of IAP proteins represents a promising approach to potentiate the efficacy of radiotherapy. The current review discusses the concept of targeting IAP proteins in combination with radiotherapy.
Highlights
The antitumor activity of radiotherapy largely depends on the activation of a cell-intrinsic program of cell death
The current review focuses on targeting Inhibitor of Apoptosis (IAP) proteins, a family of antiapoptotic proteins that play a critical role in the regulation of sensitivity and resistance of cancer cells
In vivo studies in a glioblastoma xenograft mouse model showed a synergistic suppression of tumor growth by co-administration of LBW242 radiation and Temozolomide (TMZ) [22]. These results demonstrate that the anti-glioma activity of radiotherapy and TMZ as state-of-the-art chemotherapy can be potentiated by the addition of second mitochondrial-derived activator of caspases (Smac) mimetic
Summary
The antitumor activity of radiotherapy largely depends on the activation of a cell-intrinsic program of cell death. IAP proteins can contribute to radiation resistance, since they block cell death pathways at several levels and are expressed at high levels in various cancers [7]. Several approaches have been developed to neutralize IAP proteins in human cancers in order to lower the threshold for the induction of cell death or to directly engage the apoptotic program.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
