Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies
View/ Open
Author
Broekgaarden, Mans
Weijer, Ruud
van Gulik, Thomas M.
Heger, Michal
Published Version
https://doi.org/10.1007/s10555-015-9588-7Metadata
Show full item recordCitation
Broekgaarden, Mans, Ruud Weijer, Thomas M. van Gulik, Michael R. Hamblin, and Michal Heger. 2015. “Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies.” Cancer Metastasis Reviews 34 (4): 643-690. doi:10.1007/s10555-015-9588-7. http://dx.doi.org/10.1007/s10555-015-9588-7.Abstract
Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies such as surgery, chemotherapy, and radiotherapy. PDT comprises the administration of a photosensitizer, its accumulation in tumor tissue, and subsequent irradiation of the photosensitizer-loaded tumor, leading to the localized photoproduction of reactive oxygen species (ROS). The resulting oxidative damage ultimately culminates in tumor cell death, vascular shutdown, induction of an antitumor immune response, and the consequent destruction of the tumor. However, the ROS produced by PDT also triggers a stress response that, as part of a cell survival mechanism, helps cancer cells to cope with the PDT-induced oxidative stress and cell damage. These survival pathways are mediated by the transcription factors activator protein 1 (AP-1), nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and those that mediate the proteotoxic stress response. The survival pathways are believed to render some types of cancer recalcitrant to PDT and alter the tumor microenvironment in favor of tumor survival. In this review, the molecular mechanisms are elucidated that occur post-PDT to mediate cancer cell survival, on the basis of which pharmacological interventions are proposed. Specifically, pharmaceutical inhibitors of the molecular regulators of each survival pathway are addressed. The ultimate aim is to facilitate the development of adjuvant intervention strategies to improve PDT efficacy in recalcitrant solid tumors.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661210/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993488
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)