Photodynamic Therapy As a Strategic Ally in Radiotherapy for Triple-negative Breast Cancer: the Importance of Treatment Order

Overview

Journal Breast Cancer Res Treat

Date 2025 Jan 8

PMID 39776332

Authors

Camila Ramos Silva

Daniel Perez Vieira

Anderson Zanardi de Freitas

Martha Simoes Ribeiro

Affiliations

Soon will be listed here.

Abstract

Purpose: Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models.

Methods: In vitro, PDT was combined with RT (2.5 Gy) using a porphyrin (TMPyP, 32 μmolL) and red light (660 ± 15 nm) with a dose of 50 Jcm. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels.

Results: Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response.

Conclusion: Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.

References

Bianchini G, Balko J, Mayer I, Sanders M, Gianni L . Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016; 13(11):674-690. PMC: 5461122. DOI: 10.1038/nrclinonc.2016.66. View

Al-Mahmood S, Sapiezynski J, Garbuzenko O, Minko T . Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res. 2018; 8(5):1483-1507. PMC: 6133085. DOI: 10.1007/s13346-018-0551-3. View

Bradley J, Mendenhall N . Novel Radiotherapy Techniques for Breast Cancer. Annu Rev Med. 2017; 69:277-288. DOI: 10.1146/annurev-med-042716-103422. View

He L, Lv Y, Song Y, Zhang B . The prognosis comparison of different molecular subtypes of breast tumors after radiotherapy and the intrinsic reasons for their distinct radiosensitivity. Cancer Manag Res. 2019; 11:5765-5775. PMC: 6612049. DOI: 10.2147/CMAR.S213663. View

Tan I, Dolivet G, Ceruse P, Vander Poorten V, Roest G, Rauschning W . Temoporfin-mediated photodynamic therapy in patients with advanced, incurable head and neck cancer: A multicenter study. Head Neck. 2010; 32(12):1597-604. DOI: 10.1002/hed.21368. View

Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J . Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol. 2005; 100(11):2426-30. DOI: 10.1111/j.1572-0241.2005.00318.x. View

Meulemans J, Delaere P, Vander Poorten V . Photodynamic therapy in head and neck cancer: indications, outcomes, and future prospects. Curr Opin Otolaryngol Head Neck Surg. 2019; 27(2):136-141. DOI: 10.1097/MOO.0000000000000521. View

Yano T, Wang K . Photodynamic Therapy for Gastrointestinal Cancer. Photochem Photobiol. 2019; 96(3):517-523. DOI: 10.1111/php.13206. View

Mayahi S, Neshasteh-Riz A, Pornour M, Eynali S, Montazerabadi A . Investigation of combined photodynamic and radiotherapy effects of gallium phthalocyanine chloride on MCF-7 breast cancer cells. J Biol Inorg Chem. 2019; 25(1):39-48. DOI: 10.1007/s00775-019-01730-w. View

10.

Cenklova V . Photodynamic therapy with TMPyP - Porphyrine induces mitotic catastrophe and microtubule disorganization in HeLa and G361 cells, a comprehensive view of the action of the photosensitizer. J Photochem Photobiol B. 2017; 173:522-537. DOI: 10.1016/j.jphotobiol.2017.06.029. View

11.

Colombo L, Vanzulli S, Villanueva A, Canete M, Juarranz A, Stockert J . Long-term regression of the murine mammary adenocarcinoma, LM3, by repeated photodynamic treatments using meso-tetra (4-N-methylpyridinium) porphine. Int J Oncol. 2005; 27(4):1053-9. View

12.

Silva C, Viana Cabral F, de Camargo C, Nunez S, Yoshimura T, de Lima Luna A . Exploring the effects of low-level laser therapy on fibroblasts and tumor cells following gamma radiation exposure. J Biophotonics. 2016; 9(11-12):1157-1166. DOI: 10.1002/jbio.201600107. View

13.

Tonnesen H, Mysterud I, Karlsen J, Skulberg O, Laane C, Schumacher T . Detection of singlet oxygen in blood serum samples of clinically healthy lambs and lambs suffering from alveld disease. Vet Res Commun. 2010; 34(4):347-57. DOI: 10.1007/s11259-010-9362-9. View

14.

Pereira S, Silva C, Nunez S, Ribeiro M . Safety and Clinical Impact of a Single Red Light Irradiation on Breast Tumor-Bearing Mice. Photochem Photobiol. 2020; 97(2):435-442. DOI: 10.1111/php.13338. View

15.

Sambade M, Camp J, Kimple R, Sartor C, Shields J . Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Radiother Oncol. 2009; 93(3):639-44. PMC: 2799330. DOI: 10.1016/j.radonc.2009.09.006. View

16.

Riethmuller M, Burger N, Bauer G . Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling. Redox Biol. 2015; 6:157-168. PMC: 4532730. DOI: 10.1016/j.redox.2015.07.006. View

17.

Jakimov D, Kojic V, Aleksic L, Bogdanovic G, Ajdukovic J, Djurendic E . Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells. Bioorg Med Chem. 2015; 23(22):7189-98. DOI: 10.1016/j.bmc.2015.10.015. View

18.

Dunne A, Price M, Mothersill C, McKeown S, Robson T, Hirst D . Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells. Br J Cancer. 2003; 89(12):2277-83. PMC: 2395286. DOI: 10.1038/sj.bjc.6601427. View

19.

Arroyo-Crespo J, Arminan A, Charbonnier D, Deladriere C, Palomino-Schatzlein M, Lamas-Domingo R . Characterization of triple-negative breast cancer preclinical models provides functional evidence of metastatic progression. Int J Cancer. 2019; 145(8):2267-2281. PMC: 6767480. DOI: 10.1002/ijc.32270. View

20.

Sabino V, Suarez Y, Andrade L, Lima S, Morais G, Guimaraes F . Photoacoustic for thermal diffusivity determination of fish scale: A methodology for environmental integrity monitoring. J Photochem Photobiol B. 2022; 227:112379. DOI: 10.1016/j.jphotobiol.2021.112379. View