Skip to main content

Advertisement

SpringerLink
Log in

Photodynamic therapy in cancer stem cells — state of the art

  • Review Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Despite significant efforts to control cancer progression and to improve oncology treatment outcomes, recurrence and tumor resistance are frequently observed in cancer patients. These problems are partly related to the presence of cancer stem cells (CSCs). Photodynamic therapy (PDT) has been developed as a therapeutic approach for solid tumors; however, it remains unclear how this therapy can affect CSCs. In this review, we focus on the effects of PDT on CSCs and the possible changes in the CSC population after PDT exposure. Tumor response to PDT varies according to the photosensitizer and light parameters employed, but most studies have reported the successful elimination of CSCs after PDT. However, some studies have reported that CSCs were more resistant to PDT than non-CSCs due to the increased efflux of photosensitizer molecules and the action of autophagy. Additionally, using different PDT approaches to target the CSCs resulted in increased sensitivity, reduction of sphere formation, invasiveness, stem cell phenotype, and improved response to chemotherapy. Lastly, although mainly limited to in vitro studies, PDT, combined with targeted therapies and/or chemotherapy, could successfully target CSCs in different solid tumors and promote the reduction of stemness, suggesting a promising therapeutic approach requiring evaluation in robust pre-clinical studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Keyvani-Ghamsari S, Khorsandi K, Rasul A, Zaman MK (2021) Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance. Clin Epigenetics 13:120. https://doi.org/10.1186/s13148-021-01107-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Raghav PK, Mann Z (2021) Cancer stem cells targets and combined therapies to prevent cancer recurrence. Life Sci 277:119465. https://doi.org/10.1016/j.lfs.2021.119465

    Article  CAS  PubMed  Google Scholar 

  3. Rodríguez Aguilar L, Vilchez ML, MillaSanabria LN (2021) Targeting glioblastoma stem cells: the first step of photodynamic therapy. Photodiagnosis Photodyn Ther 36:102585. https://doi.org/10.1016/j.pdpdt.2021.102585

    Article  CAS  PubMed  Google Scholar 

  4. Wei M-F, Chen M-W, Chen K-C, Lou P-J, Lin SY-F, Hung S-C, Hsiao M, Yao C-J, Shieh M-J (2014) Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells. Autophagy 10:1179–1192. https://doi.org/10.4161/auto.28679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhang Z-J, Wang K-P, Mo J-G, Xiong L, Wen Y (2020) Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species. World J Stem Cells 12:562–584. https://doi.org/10.4252/wjsc.v12.i7.562

    Article  PubMed  PubMed Central  Google Scholar 

  6. Takeshima H, Ushijima T (2019) Accumulation of genetic and epigenetic alterations in normal cells and cancer risk. NPJ Precis Oncol 3:7. https://doi.org/10.1038/s41698-019-0079-0

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  8. Nguyen LV, Vanner R, Dirks P, Eaves CJ (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12:133–143. https://doi.org/10.1038/nrc3184

    Article  CAS  PubMed  Google Scholar 

  9. O’Connor ML, Xiang D, Shigdar S, Macdonald J, Li Y, Wang T, Pu C, Wang Z, Qiao L, Duan W (2014) Cancer stem cells: a contentious hypothesis now moving forward. Cancer Lett 344:180–187. https://doi.org/10.1016/j.canlet.2013.11.012

    Article  CAS  PubMed  Google Scholar 

  10. Rich JN (2016) Cancer stem cells: understanding tumor hierarchy and heterogeneity. Medicine 95:S2–S7. https://doi.org/10.1097/MD.0000000000004764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tomasetti C, Vogelstein B (1979) Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2015(347):78–81. https://doi.org/10.1126/science.1260825

    Article  CAS  Google Scholar 

  12. Nimmakayala RK, Batra SK, Ponnusamy MP (2019) Unraveling the journey of cancer stem cells from origin to metastasis. Biochimica et Biophysica Acta (BBA)- Reviews on Cancer 1871:50–63. https://doi.org/10.1016/j.bbcan.2018.10.006

    Article  CAS  PubMed  Google Scholar 

  13. Zhang R, Tu J, Liu S (2022) Novel molecular regulators of breast cancer stem cell plasticity and heterogeneity. Semin Cancer Biol 82:11–25. https://doi.org/10.1016/j.semcancer.2021.03.008

    Article  CAS  PubMed  Google Scholar 

  14. Reid PA, Wilson P, Li Y, Marcu LG, Bezak E (2017) Current understanding of cancer stem cells: review of their radiobiology and role in head and neck cancers. Head Neck 39:1920–1932. https://doi.org/10.1002/hed.24848

    Article  PubMed  Google Scholar 

  15. Atiya H, Frisbie L, Pressimone C, Coffman L (2020) Mesenchymal stem cells in the tumor microenvironment. 31–42.

  16. Plaks V, Kong N, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16:225–238. https://doi.org/10.1016/j.stem.2015.02.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Manhas J, Bhattacharya A, Agrawal SK, Gupta B, Das P, Deo SVS, Pal S, Sen S (2016) Characterization of cancer stem cells from different grades of human colorectal cancer. Tumor Biol 37:14069–14081. https://doi.org/10.1007/s13277-016-5232-6

    Article  CAS  Google Scholar 

  18. Thiery JP, Acloque H, Huang RYJ, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890. https://doi.org/10.1016/j.cell.2009.11.007

    Article  CAS  PubMed  Google Scholar 

  19. Charles N, Ozawa T, Squatrito M, Bleau A-M, Brennan CW, Hambardzumyan D, Holland EC (2010) Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 6:141–152. https://doi.org/10.1016/j.stem.2010.01.001

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Z, Dong Z, Lauxen IS, Filho MS, Nör JE (2014) Endothelial cell-secreted EGF induces epithelial to mesenchymal transition and endows head and neck cancer cells with stem-like phenotype. Cancer Res 74:2869–2881. https://doi.org/10.1158/0008-5472.CAN-13-2032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ricardo S, Vieira AF, Gerhard R, Leitao D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J (2011) Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol 64:937–946. https://doi.org/10.1136/jcp.2011.090456

    Article  PubMed  Google Scholar 

  22. Li R, Wu X, Wei H, Tian S (2013) Characterization of side population cells isolated from the gastric cancer cell line SGC-7901. Oncol Lett 5:877–883. https://doi.org/10.3892/ol.2013.1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou J-Y, Chen M, Ma L, Wang X, Chen Y-G, Liu S-L (2016) Role of CD44high/CD133high HCT-116 cells in the tumorigenesis of colon cancer. Oncotarget 7:7657–7666

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lv X, Wang Y, Song Y, Pang X, Li H (2016) Association between ALDH1+/CD133+ stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma. Oncol Lett 11:1750–1756. https://doi.org/10.3892/ol.2016.4145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Brugnoli F, Grassilli S, Piazzi M, Palomba M, Nika E, Bavelloni A, Capitani S, Bertagnolo V (2013) In triple negative breast tumor cells, PLC-Β2 promotes the conversion of CD133high to CD133low phenotype and reduces the CD133-related invasiveness. Mol Cancer 12:165. https://doi.org/10.1186/1476-4598-12-165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci 104:973–978. https://doi.org/10.1073/pnas.0610117104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Biddle A, Liang X, Gammon L, Fazil B, Harper LJ, Emich H, Costea DE, Mackenzie IC (2011) Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res 71:5317–5326. https://doi.org/10.1158/0008-5472.CAN-11-1059

    Article  CAS  PubMed  Google Scholar 

  28. Shibue T, Weinberg RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 14:611–629. https://doi.org/10.1038/nrclinonc.2017.44

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pirozzi G, Tirino V, Camerlingo R, Franco R, la Rocca A, Liguori E, Martucci N, Paino F, Normanno N, Rocco G (2011) Epithelial to mesenchymal transition by TGFβ-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. Plos One 6:e21548. https://doi.org/10.1371/journal.pone.0021548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mani SA, Guo W, Liao M-J, Ng Eaton E, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715. https://doi.org/10.1016/j.cell.2008.03.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Celià-Terrassa T, Jolly MK (2020) Cancer stem cells and epithelial-to-mesenchymal transition in cancer metastasis. Cold Spring Harb Perspect Med 10:a036905. https://doi.org/10.1101/cshperspect.a036905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bao B, Ahmad A, Azmi AS, Ali S, Sarkar FH (2013) Overview of cancer stem cells (CSCs) and mechanisms of their regulation: implications for cancer therapy. Curr Protoc Pharmacol 61 https://doi.org/10.1002/0471141755.ph1425s61

  33. Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7:834–846. https://doi.org/10.1038/nrc2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang T, Shigdar S, Gantier MP, Hou Y, Wang L, Li Y, al hamaileh H, Yin W, Zhou S-F, Zhao X et al (2015) Cancer stem cell targeted therapy: progress amid controversies. Oncotarget 6:44191–44206. https://doi.org/10.18632/oncotarget.6176

    Article  PubMed  PubMed Central  Google Scholar 

  35. Steinbichler TB, Dudás J, Skvortsov S, Ganswindt U, Riechelmann H, Skvortsova I-I (2018) Therapy resistance mediated by cancer stem cells. Semin Cancer Biol 53:156–167. https://doi.org/10.1016/j.semcancer.2018.11.006

    Article  CAS  PubMed  Google Scholar 

  36. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D, Lam JS, Ailles LE, Wong M et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:780–783. https://doi.org/10.1038/nature07733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Skvortsova I, Debbage P, Kumar V, Skvortsov S (2015) Radiation resistance: cancer stem cells (cscs) and their enigmatic pro-survival signaling. Semin Cancer Biol 35:39–44. https://doi.org/10.1016/j.semcancer.2015.09.009

    Article  CAS  PubMed  Google Scholar 

  38. Nassar D, Blanpain C (2016) Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol 11:47–76. https://doi.org/10.1146/annurev-pathol-012615-044438

    Article  CAS  PubMed  Google Scholar 

  39. Spikes JD (1991) The origin and meaning of the term “photodynamic” (as used in “photodynamic therapy”, for example). J Photochem Photobiol B 9:369–371. https://doi.org/10.1016/1011-1344(91)80172-E

    Article  CAS  PubMed  Google Scholar 

  40. Kessel D (2019) Photodynamic therapy: a brief history. J Clin Med 8:1581. https://doi.org/10.3390/jcm8101581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gunaydin G, Gedik ME, Ayan S (2021) Photodynamic therapy—current limitations and novel approaches. Front Chem 9 https://doi.org/10.3389/fchem.2021.691697

  42. Mallidi S, Anbil S, Bulin A-L, Obaid G, Ichikawa M, Hasan T (2016) Beyond the barriers of light penetration: strategies, perspectives and possibilities for photodynamic therapy. Theranostics 6:2458–2487. https://doi.org/10.7150/thno.16183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dolmans DEJGJ, Fukumura D, Jain RK (2003) Photodynamic therapy for cancer. Nat Rev Cancer 3:380–387. https://doi.org/10.1038/nrc1071

    Article  CAS  PubMed  Google Scholar 

  44. van Straten D, Mashayekhi V, de Bruijn H, Oliveira S, Robinson D (2017) Oncologic photodynamic therapy: basic principles, current clinical status and future directions. Cancers (Basel) 9:19. https://doi.org/10.3390/cancers9020019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kou J, Dou D, Yang L (2017) Porphyrin photosensitizers in photodynamic therapy and its applications. Oncotarget 8:81591–81603. https://doi.org/10.18632/oncotarget.20189

    Article  PubMed  PubMed Central  Google Scholar 

  46. de Visscher SAHJ, Kaščáková S, de Bruijn HS, van den Heuvel A, van der Amelink PA, Sterenborg HJCM, Robinson DJ, Roodenburg JLN, Witjes MJH (2011) Fluorescence localization and kinetics of MTHPC and liposomal formulations of MTHPC in the Window-chamber tumor model. Lasers Surg Med 43:528–536. https://doi.org/10.1002/lsm.21082

    Article  PubMed  Google Scholar 

  47. Bellnier DA, Greco WR, Nava H, Loewen GM, Oseroff AR, Dougherty TJ (2006) Mild skin photosensitivity in cancer patients following injection of photochlor (2-[1-hexyloxyethyl]-2-Devinyl pyropheophorbide-a; HPPH) for photodynamic therapy. Cancer Chemother Pharmacol 57:40–45. https://doi.org/10.1007/s00280-005-0015-6

    Article  CAS  PubMed  Google Scholar 

  48. Robertson CA, Evans DH, Abrahamse H (2009) Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B 96:1–8. https://doi.org/10.1016/j.jphotobiol.2009.04.001

    Article  CAS  PubMed  Google Scholar 

  49. Abrahamse H, Hamblin MR (2016) New photosensitizers for photodynamic therapy. Biochem J 473:347–364. https://doi.org/10.1042/BJ20150942

    Article  CAS  PubMed  Google Scholar 

  50. Lai HW, Nakayama T, Ogura S (2021) Key Transporters leading to specific protoporphyrin ix accumulation in cancer cell following administration of aminolevulinic acid in photodynamic therapy/diagnosis. Int J Clin Oncol 26:26–33. https://doi.org/10.1007/s10147-020-01766-y

    Article  CAS  PubMed  Google Scholar 

  51. Kessel D (1992) The role of low-density lipoprotein in the biodistribution of photosensitizing agents. J Photochem Photobiol B 14:261–262. https://doi.org/10.1016/1011-1344(92)85103-2

    Article  CAS  PubMed  Google Scholar 

  52. Bostad M, Berg K, Høgset A, Skarpen E, Stenmark H, Selbo PK (2013) Photochemical internalization (pci) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. J Control Release 168:317–326. https://doi.org/10.1016/j.jconrel.2013.03.023

    Article  CAS  PubMed  Google Scholar 

  53. Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR (2011) Cell death pathways in photodynamic therapy of cancer. Cancers (Basel) 3:2516–2539. https://doi.org/10.3390/cancers3022516

    Article  CAS  PubMed  Google Scholar 

  54. Plaetzer K, Kiesslich T, Verwanger T, Krammer B (2003) The modes of cell death induced by PDT: an overview. Med Laser Appl 18:7–19. https://doi.org/10.1078/1615-1615-00082

    Article  Google Scholar 

  55. St. Denis TG, Aziz K, Waheed AA, Huang Y-Y, Sharma SK, Mroz P, Hamblin MR (2011) Combination approaches to potentiate immune response after photodynamic therapy for cancer. Photochem Photobiol Sci 10:792–801. https://doi.org/10.1039/c0pp00326c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Alzeibak R, Mishchenko TA, Shilyagina NY, Balalaeva IV, Vedunova MV, Krysko DV (2021) Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future. J Immunother Cancer 9:e001926. https://doi.org/10.1136/jitc-2020-001926

    Article  PubMed  PubMed Central  Google Scholar 

  57. Garg AD, Krysko DV, Vandenabeele P, Agostinis P (2012) Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin. Cancer Immunol Immunother 61:215–221. https://doi.org/10.1007/s00262-011-1184-2

    Article  CAS  PubMed  Google Scholar 

  58. Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek AJM et al (2012) A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J 31:1062–1079. https://doi.org/10.1038/emboj.2011.497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Trempolec N, Doix B, Degavre C, Brusa D, Bouzin C, Riant O, Feron O (2020) Photodynamic therapy-based dendritic cell vaccination suited to treat peritoneal mesothelioma. Cancers (Basel) 12:545. https://doi.org/10.3390/cancers12030545

    Article  CAS  PubMed  Google Scholar 

  60. Li W, Yang J, Luo L, Jiang M, Qin B, Yin H, Zhu C, Yuan X, Zhang J, Luo Z et al (2019) Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death. Nat Commun 10:3349. https://doi.org/10.1038/s41467-019-11269-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Triesscheijn M, Ruevekamp M, Aalders M, Baas P, Stewart FA (2005) Outcome of MTHPC mediated photodynamic therapy is primarily determined by the vascular response. Photochem Photobiol 81:1161. https://doi.org/10.1562/2005-04-04-RA-474

    Article  CAS  PubMed  Google Scholar 

  62. Lamberti MJ, Morales Vasconsuelo AB, Ferrara MG, Rumie Vittar NB (2020) Recapitulation of hypoxic tumor–stroma microenvironment to study photodynamic therapy implications. Photochem Photobiol 96:897–905. https://doi.org/10.1111/php.13220

    Article  CAS  PubMed  Google Scholar 

  63. Ahn PH, Finlay JC, Gallagher-Colombo SM, Quon H, O’Malley BW, Weinstein GS, Chalian A, Malloy K, Sollecito T, Greenberg M et al (2018) Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy. Photodiagnosis Photodyn Ther 21:28–35. https://doi.org/10.1016/j.pdpdt.2017.10.015

    Article  CAS  PubMed  Google Scholar 

  64. Lamberti MJ, Pansa MF, Vera RE, Fernández-Zapico ME, RumieVittar NB, Rivarola VA (2017) Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy. Plos One 12:e0177801. https://doi.org/10.1371/journal.pone.0177801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Martins WK, Belotto R, Silva MN, Grasso D, Suriani MD, Lavor TS, Itri R, Baptista MS, Tsubone TM (2021) Autophagy regulation and photodynamic therapy: insights to improve outcomes of cancer treatment. Front Oncol 10 https://doi.org/10.3389/fonc.2020.610472

  66. Qi XS, Pajonk F, McCloskey S, Low DA, Kupelian P, Steinberg M, Sheng K (2017) Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation. Radiother Oncol 124:455–461. https://doi.org/10.1016/j.radonc.2017.08.019

    Article  PubMed  PubMed Central  Google Scholar 

  67. Wang D, Lu P, Zhang H, Luo M, Zhang X, Wei X, Gao J, Zhao Z, Liu C (2014) Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget 5:10803–10815. https://doi.org/10.18632/oncotarget.2506

    Article  PubMed  PubMed Central  Google Scholar 

  68. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci 100:3983–3988. https://doi.org/10.1073/pnas.0530291100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567. https://doi.org/10.1016/j.stem.2007.08.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Badve S, Nakshatri H (2006) CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 8:R59. https://doi.org/10.1186/bcr1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chang C-J, Hung M-C (2012) The role of EZH2 in tumour progression. Br J Cancer 106:243–247. https://doi.org/10.1038/bjc.2011.551

    Article  CAS  PubMed  Google Scholar 

  72. Selbo PK, Weyergang A, Eng MS, Bostad M, Mælandsmo GM, Høgset A, Berg K (2012) Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug. J Control Release 159:197–203. https://doi.org/10.1016/j.jconrel.2012.02.003

    Article  CAS  PubMed  Google Scholar 

  73. Gaio E, Conte C, Esposito D, Reddi E, Quaglia F, Moret F (2020) CD44 targeting mediated by polymeric nanoparticles and combination of chlorine TPCS2a-PDT and docetaxel-chemotherapy for efficient killing of breast differentiated and stem cancer cells in vitro. Cancers (Basel) 12:278. https://doi.org/10.3390/cancers12020278

    Article  CAS  PubMed  Google Scholar 

  74. Chen K, Shen S, Zhao G, Cao Z, Yang X, Wang J (2018) Simultaneous elimination of cancer stem cells and bulk cancer cells by cationic-lipid-assisted nanoparticles for cancer therapy. Nano Res 11:4183–4198. https://doi.org/10.1007/s12274-018-2007-y

    Article  CAS  Google Scholar 

  75. Hu Z, Xu J, Cheng J, McMichael E, Yu L, Carson WE (2017) Targeting tissue factor as a novel therapeutic Oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer. Oncotarget 8:1481–1494. https://doi.org/10.18632/oncotarget.136

    Article  PubMed  Google Scholar 

  76. Raschpichler M, Preis E, Pinnapireddy SR, Baghdan E, Pourasghar M, Schneider M, Bakowsky U (2020) Photodynamic inactivation of circulating tumor cells: an innovative approach against metastatic cancer. Eur J Pharm Biopharm 157:38–46. https://doi.org/10.1016/j.ejpb.2020.10.003

    Article  CAS  PubMed  Google Scholar 

  77. Kim HS, Kim K, Ryoo S-B, Seo JH, Kim SY, Park JW, Kim MA, Hong KS, Jeong CW, Song YS (2015) Conventional versus nerve-sparing radical surgery for cervical cancer: a meta-analysis. J Gynecol Oncol 26:100. https://doi.org/10.3802/jgo.2015.26.2.100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Allanson ER, Powell A, Bulsara M, Lee HL, Denny L, Leung Y, Cohen P (2019) Morbidity after surgical management of cervical cancer in low and middle income countries: a systematic review and meta-analysis. Plos One 14:e0217775. https://doi.org/10.1371/journal.pone.0217775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Muroya T, Kawasaki K, Suehiro Y, Kunugi T, Umayahara K, Akiya T, Iwabuchi H, Sakunaga H, Sakamoto M, Sugishita T et al (1999) Application of PDT for uterine cervical cancer. Diagn Ther Endosc 5:183–190. https://doi.org/10.1155/DTE.5.183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Pkhakadze G, Bokhua Z, Asatiani T, Muzashvili T, Burkadze G (2021) Stem cell index in the progression of cervical intraepithelial neoplasia. Georgian Med News 157–164.

  81. Huang Y, Luo F (2021) Elevated microRNA-130b-5p or silenced ELK1 inhibits self-renewal ability, proliferation, migration, and invasion abilities, and promotes apoptosis of cervical cancer stem cells. IUBMB Life 73:118–129. https://doi.org/10.1002/iub.2409

    Article  CAS  PubMed  Google Scholar 

  82. Huang R, Rofstad EK (2017) Cancer stem cells (CSCs), cervical CSCs and targeted therapies. Oncotarget 8:35351–35367. https://doi.org/10.18632/oncotarget.10169

    Article  PubMed  Google Scholar 

  83. Mendoza-Almanza G, Ortíz-Sánchez E, Rocha-Zavaleta L, Rivas-Santiago C, Esparza-Ibarra E, Olmos J (2019) Cervical cancer stem cells and other leading factors associated with cervical cancer development. Oncol Lett 18:3423–3432. https://doi.org/10.3892/ol.2019.10718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Schmidt S, Schultes B, Wagner U, Oehr P, Decleer W, Lubaschowski H, Biersack HJ, Krebs D (1991) Photodynamic laser therapy of carcinomas — effects of five different photosensitizers in the colony-forming assay. Arch Gynecol Obstet 249:9–14. https://doi.org/10.1007/BF02390701

    Article  CAS  PubMed  Google Scholar 

  85. Chizenga EP, Chandran R, Abrahamse H (2019) Photodynamic therapy of cervical cancer by eradication of cervical cancer cells and cervical cancer stem cells. Oncotarget 10:4380–4396. https://doi.org/10.18632/oncotarget.27029

    Article  PubMed  PubMed Central  Google Scholar 

  86. Fattahi F, Saeednejad Zanjani L, Vafaei S, Habibi Shams Z, Kiani J, Naseri M, Gheytanchi E, Madjd Z (2021) Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis. Diagn Pathol 16:26. https://doi.org/10.1186/s13000-021-01088-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mao X, Zhang X, Zheng X, Chen Y, Xuan Z, Huang P (2021) Curcumin suppresses LGR5(+) colorectal cancer stem cells by inducing autophagy and via repressing tfap2a-mediated ECM pathway. J Nat Med 75:590–601. https://doi.org/10.1007/s11418-021-01505-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110. https://doi.org/10.1038/nature05372

    Article  CAS  PubMed  Google Scholar 

  89. Catalano V, di Franco S, Iovino F, Dieli F, Stassi G, Todaro M (2012) CD133 as a target for colon cancer. Expert Opin Ther Targets 16:259–267. https://doi.org/10.1517/14728222.2012.667404

    Article  CAS  PubMed  Google Scholar 

  90. Wei M-F, Han S-Y, Yang S-J, Lin F-H, Hung S-C, Shieh M-J (2009) Cell death of colorectal cancer stem-like cell was induced by photodynamic therapy with protoporphyrin IX Taiwan Academic Institutional Repository NTUR 44

  91. Cogno IS, Gilardi P, Comini L, Núñez-Montoya SC, Cabrera JL, Rivarola VA (2020) Natural photosensitizers in photodynamic therapy: in vitro activity against monolayers and spheroids of human colorectal adenocarcinoma SW480 Cells. Photodiagnosis Photodyn Ther 31:101852. https://doi.org/10.1016/j.pdpdt.2020.101852

    Article  CAS  PubMed  Google Scholar 

  92. Ibarra AMC, Cecatto RB, Motta LJ, dos Santos Franco AL, Fátima Teixeira Silva D, Nunes FD, Hamblin MR, Rodrigues MFSD (2022) Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers. Lasers Med Sci 37:1441–1470. https://doi.org/10.1007/s10103-021-03462-3

    Article  PubMed  Google Scholar 

  93. Liang J, Yang B, Zhou X, Han Q, Zou J, Cheng L (2021) Stimuli-responsive drug delivery systems for head and neck cancer therapy. Drug Deliv 28:272–284. https://doi.org/10.1080/10717544.2021.1876182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ikeda H, Tobita T, Ohba S, Uehara M, Asahina I (2013) Treatment outcome of photofrin-based photodynamic therapy for T1 and T2 oral squamous cell carcinoma and dysplasia. Photodiagnosis Photodyn Ther 10:229–235. https://doi.org/10.1016/j.pdpdt.2013.01.006

    Article  CAS  PubMed  Google Scholar 

  95. Adams A, Warner K, Pearson AT, Zhang Z, Kim HS, Mochizuki D, Basura G, Helman J, Mantesso A, Castilho RM et al (2015) ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas. Oncotarget 6:26633–26650. https://doi.org/10.18632/oncotarget.5782

    Article  PubMed  PubMed Central  Google Scholar 

  96. Yu C-H, Yu C-C (2014) Photodynamic therapy with 5-aminolevulinic acid (ALA) impairs tumor initiating and chemo-resistance property in head and neck cancer-derived cancer stem cells. Plos One 9:e87129. https://doi.org/10.1371/journal.pone.0087129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Peng Y, He G, Tang D, Xiong L, Wen Y, Miao X, Hong Z, Yao H, Chen C, Yan S et al (2017) Lovastatin inhibits cancer stem cells and sensitizes to chemo- and photodynamic therapy in nasopharyngeal carcinoma. J Cancer 8:1655–1664. https://doi.org/10.7150/jca.19100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Momen-Heravi F, Bala S (2018) Emerging role of non-coding RNA in oral cancer. Cell Signal 42:134–143. https://doi.org/10.1016/j.cellsig.2017.10.009

    Article  CAS  PubMed  Google Scholar 

  99. Fang C-Y, Chen P-Y, Ho DC-Y, Tsai L-L, Hsieh P-L, Lu M-Y, Yu C-C, Yu C-H (2018) MiR-145 mediates the anti-cancer stemness effect of photodynamic therapy with 5-aminolevulinic acid (ALA) in oral cancer cells. J Formos Med Assoc 117:738–742. https://doi.org/10.1016/j.jfma.2018.05.018

    Article  CAS  PubMed  Google Scholar 

  100. Yu C-C, Tsai L-L, Wang M-L, Yu C-H, Lo W-L, Chang Y-C, Chiou G-Y, Chou M-Y, Chiou S-H (2013) MiR145 Targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6–mediated paracrine effects in head and neck cancer. Cancer Res 73:3425–3440. https://doi.org/10.1158/0008-5472.CAN-12-3840

    Article  CAS  PubMed  Google Scholar 

  101. Pinto MAF, Ferreira CBR, de Lima BES, Molon ÂC, Ibarra AMC, Cecatto RB, dos Santos Franco AL, Rodrigues MFSD (2022) Effects of 5-ALA mediated photodynamic therapy in oral cancer stem cells. J Photochem Photobiol B 235:112552. https://doi.org/10.1016/j.jphotobiol.2022.112552

    Article  CAS  PubMed  Google Scholar 

  102. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401. https://doi.org/10.1038/nature03128

    Article  CAS  PubMed  Google Scholar 

  103. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen H-J (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre Phase III Trial. Lancet Oncol 7:392–401. https://doi.org/10.1016/S1470-2045(06)70665-9

    Article  CAS  PubMed  Google Scholar 

  104. Eljamel MS, Goodman C, Moseley H (2008) ALA and Photofrin® fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomised controlled trial. Lasers Med Sci 23:361–367. https://doi.org/10.1007/s10103-007-0494-2

    Article  PubMed  Google Scholar 

  105. Wang W, Tabu K, Hagiya Y, Sugiyama Y, Kokubu Y, Murota Y, Ogura S, Taga T (2017) Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation. Sci Rep 7:42070. https://doi.org/10.1038/srep42070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fujishiro T, Nonoguchi N, Pavliukov M, Ohmura N, Kawabata S, Park Y, Kajimoto Y, Ishikawa T, Nakano I, Kuroiwa T (2018) 5-Aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents. Photodiagnosis Photodyn Ther 24:58–68. https://doi.org/10.1016/j.pdpdt.2018.07.004

    Article  CAS  PubMed  Google Scholar 

  107. Schimanski A, Ebbert L, Sabel MC, Finocchiaro G, Lamszus K, Ewelt C, Etminan N, Fischer JC, Sorg RV (2016) Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment. J Photochem Photobiol B 163:203–210. https://doi.org/10.1016/j.jphotobiol.2016.08.043

    Article  CAS  PubMed  Google Scholar 

  108. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323. https://doi.org/10.1016/j.stem.2007.06.002

    Article  CAS  PubMed  Google Scholar 

  109. Kawai N, Hirohashi Y, Ebihara Y, Saito T, Murai A, Saito T, Shirosaki T, Kubo T, Nakatsugawa M, Kanaseki T et al (2019) ABCG2 expression is related to low 5-ala photodynamic diagnosis (PDD) efficacy and cancer stem cell phenotype, and suppression of ABCG2 improves the efficacy of PDD. Plos One 14:e0216503. https://doi.org/10.1371/journal.pone.0216503

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Graphical abstract was created with Biorender.com under premium subscription copyright.

Funding

This research was funded by the São Paulo Research Foundation (FAPESP) (grant number 2018/08540–8; 2019/09465); the Coordination for the Improvement of Higher Education Personnel (CAPES) (Finance code 001, grant number 88882.365373/2019–01); and the National Council for Scientific and Technological Development (CNPq) (grant number 141675/2018–7). US NIH Grants R01AI050875 and R21AI121700 supported MRH.

Author information

Authors and Affiliations

  1. Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University - UNINOVE, São Paulo, Brazil

    Ana Melissa C. Ibarra, Cássia B. R. Ferreira, Adriana Lino-Dos- Santos Franco, Rebeca B. Cecatto & Maria Fernanda S. D. Rodrigues

  2. School of Dentistry, University of São Paulo – FOUSP, São Paulo, Brazil

    Emilia Maria G. Aguiar, Juliana M. Siqueira, Luciana Corrêa & Fabio D. Nunes

  3. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Johannesburg, South Africa

    Michael R. Hamblin

Authors
  1. Ana Melissa C. Ibarra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilia Maria G. Aguiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cássia B. R. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juliana M. Siqueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luciana Corrêa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabio D. Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adriana Lino-Dos- Santos Franco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rebeca B. Cecatto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael R. Hamblin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Fernanda S. D. Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, M.F.S.D.R.; formal analysis, A.M.C. and C.B.R.F. and L.C. and F.D.N. and A.L.S.F. and R.B.C. and M.R.H. and M.F.S.D.R.; data curation, A.M.C. and E.M.G.A. and C.B.R.F. and J.M.S. and L.C. and F.D.N. and A.L.S.F. and R.B.C. and M.R.H.; writing, original draft preparation, A.M.C. and E.M.G.A. and L.C. and F.D.N., M.R.H. and M.F.S.D.R; writing, review and editing, M.F.S.D.R and E.M.G.A. and J.M.S.; supervision, M.F.S.D.R; funding acquisition, M.F.S.D.R. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Maria Fernanda S. D. Rodrigues.

Ethics declarations

Conflict of interest

Michael R. Hamblin declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc., Cleveland, OH; Hologenix Inc., Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc., Minneapolis-St. Paul, MN; Sunlighten, Kansas City, MO; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany; Klox Asia, Guangzhou, China. Stockholding: Niraxx Light Therapeutics, Inc., Irvine CA; JelikaLite Corp, New York, NY. The other authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ibarra, A.M.C., Aguiar, E.M.G., Ferreira, C.B.R. et al. Photodynamic therapy in cancer stem cells — state of the art. Lasers Med Sci 38, 251 (2023). https://doi.org/10.1007/s10103-023-03911-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10103-023-03911-1

Keywords

Search

Navigation