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Photodynamic therapy to treat breast cancer: proof of concept pre-clinical studies

Grant number: 16/04676-7
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2016
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Leticia Labriola
Grantee:Ancély Ferreira dos Santos
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/50680-5 - Photosensitization in life sciences, AP.TEM
Associated scholarship(s):17/23914-9 - Exploring the immunogenic potential of photodynamic therapy, BE.EP.PD


Breast cancer is the second leading cause of cancer-related deaths among women in the world. Concentered efforts have been made in recent years to develop therapies that are able to treat various forms of breast cancer more effectively. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as hormone or growth factor receptors. However, these agents are ineffective in the treatment of metastatic disease, which is characterized by the presence of triple-negative breast cancers (TNBC). A promising alternative treatment is photodynamic therapy (PDT), consisting in tissue destruction by visible light in the presence of a photosensitizer substance and oxygen. Previous results have shown that PDT using methylene blue, as a photosensitizer (MB-PDT) is able to selectively eliminate tumor breast cells in vitro models of cultured cells in monolayer or in spheroids, being more aggressive with the triple negative ones. In order to further validate this therapy, it is essential to continue the evaluation of the effectiveness of MB-PDT in tumors in vivo. Therefore, in the present project, we set out to perform pre-clinical trials for MB-PDT, analyzing its effectiveness in activating the immune system and completely killing the tumoral cells, minimizing the chances of recurrence. It is important to note that, preliminary data indicate that the MB-PDT has potential to induce a pro-inflammatory response against tumoral cells, demonstrating the importance of continuing these studies. From a translational point of view, this project will help to clarify yet unknown molecular mechanisms and to demonstrate the efficacy of MB-PDT, both fundamental to the development and feasibility of this strategy for treatment of more aggressive tumors.

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DOS SANTOS, ANCELY F.; DE ALMEIDA, DARIA RAQUEL Q.; TERRA, LETICIA F.; WAILEMANN, ROSANGELA A. M.; GOMES, VINICIUS M.; ARINI, GABRIEL S.; RAVAGNANI, FELIPE G.; BAPTISTA, MAURICIO S.; LABRIOLA, LETICIA. Fluence Rate Determines PDT Efficiency in Breast Cancer Cells Displaying Different GSH Levels. Photochemistry and Photobiology, v. 96, n. 3, SI, . (13/07937-8, 16/04676-7, 17/03618-6, 19/09517-2)
WAILEMANN, ROSANGELA A. M.; TERRA, LETICIA F.; OLIVEIRA, TALITA C.; DOS SANTOS, ANCELY F.; GOMES, VINICIUS M.; LABRIOLA, LETICIA. Heat shock protein B1 is required for the prolactin-induced cytoprotective effects on pancreatic islets. Molecular and Cellular Endocrinology, v. 477, p. 39-47, . (14/17974-0, 14/02745-6, 13/13914-0, 13/07029-4, 16/04676-7, 17/03618-6)
GOMES, VINICIUS M.; WAILEMANN, ROSANGELA A. M.; ARINI, GABRIEL S.; OLIVEIRA, TALITA C.; ALMEIDA, DARIA R. Q.; DOS SANTOS, ANCELY F.; TERRA, LETICIA F.; LORTZ, STEPHAN; LABRIOLA, LETICIA. HSPB1 Is Essential for Inducing Resistance to Proteotoxic Stress in Beta-Cells. CELLS, v. 10, n. 9, . (13/07937-8, 19/09517-2, 16/04676-7)
MULE, SIMON NGAO; GOMES, VINICIUS DE MORAIS; WAILEMANN, ROSANGELA A. M.; MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; LARSEN, MARTIN R.; LABRIOLA, LETICIA; PALMISANO, GIUSEPPE. HSPB1 influences mitochondrial respiration in ER-stressed beta cells. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 9, . (17/04032-5, 14/02745-6, 17/03618-6, 18/18257-1, 16/04676-7, 20/04923-0, 16/14845-0, 13/07937-8, 18/15549-1, 21/00507-4)
DOS SANTOS, ANCELY F.; INAGUE, ALEX; ARINI, GABRIEL S.; TERRA, LETICIA F.; WAILEMANN, ROSANGELA A. M.; PIMENTEL, ANDRE C.; YOSHINAGA, MARCOS Y.; SILVA, RICARDO R.; SEVERINO, DIVINOMAR; DE ALMEIDA, DARIA RAQUEL Q.; et al. Distinct photo-oxidation-induced cell death pathways lead to selective killing of human breast cancer cells. CELL DEATH & DISEASE, v. 11, n. 12, . (19/09517-2, 17/13804-1, 19/05026-4, 16/04676-7, 17/23914-9, 17/18922-2, 17/03618-6, 15/02654-3, 13/07937-8)

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