Modeling Epidermal Growth Factor Inhibitor-mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture.
Journal
Photochemistry and photobiology
ISSN: 1751-1097
Titre abrégé: Photochem Photobiol
Pays: United States
ID NLM: 0376425
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
27
07
2018
accepted:
19
11
2018
pubmed:
1
12
2018
medline:
2
5
2019
entrez:
1
12
2018
Statut:
ppublish
Résumé
We have demonstrated that lung-sparing surgery with intraoperative photodynamic therapy (PDT) achieves remarkably extended survival for patients with malignant pleural mesothelioma (MPM). Nevertheless, most patients treated using this approach experience local recurrence, so it is essential to identify ways to enhance tumor response. We previously reported that PDT transiently activates EGFR/STAT3 in lung and ovarian cancer cells and inhibiting EGFR via erlotinib can increase PDT sensitivity. Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response. Since extracellular matrix (ECM) proteins accrued during stroma development can alter EGF signaling within tumors, we have characterized novel 3D models of MPM to determine their response to erlotinib combined with Photofrin-PDT. Our MPM cell lines formed a range of acinar phenotypes when grown on ECM gels, recapitulating the locally invasive phenotype of MPM in pleura and endothoracic fascia. Using these models, we confirmed that EGFR inhibition increases PDT cytotoxicity. Together with emerging evidence that EGFR inhibition may improve survival of lung cancer patients through immunologic and direct cell killing mechanisms, these results suggest erlotinib-enhanced PDT may significantly improve outcomes for MPM patients.
Identifiants
pubmed: 30499112
doi: 10.1111/php.13067
pmc: PMC6553615
mid: NIHMS999810
doi:
Substances chimiques
Antineoplastic Agents
0
Epidermal Growth Factor
62229-50-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-405Subventions
Organisme : NCI NIH HHS
ID : P01 CA087971
Pays : United States
Organisme : Penn Translational Centers for Excellence in Mesothelioma Research and Radiation Oncology
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 The American Society of Photobiology.
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