Photodynamic therapy for melanoma: a multifaceted anti-cancer treatment against malignant melanoma

International Journal of Biophotonics and Biomedical Engineering

مقاله 5، دوره 1، شماره 1، مهر 2021، صفحه 35-50   

نوع مقاله: Timely in-depth review

شناسه دیجیتال (DOI): 10.30495/ijbbo.2021.686476

نویسندگان

Neda Rajabi¹؛ Mahsa Gholizadeh¹؛ Sanaz Baghban Khoshechin¹؛ Mohammad Amin Doustvandi¹؛ Fateme Mohammadnejad¹؛ Habib Tajalli²؛ Behzad Baradaran^{* 1}

¹Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

²Biophotonics Research Center,Tabriz Branch, Islamic Azad University

چکیده

The treatment of patients with malignant melanoma remains complex and unsatisfactory. Conventional treatment strategies have been approximately ineffective. Dacarbazine (DTIC) is identified as one of the most effective chemotherapy drugs against melanoma with a response rate of around 15–20%. Numerous patients with melanoma who primarily respond to surgery subsequently relapse. Obviously, there is an essential need for better identification, and the improvement of potential treatments is warranted. One such treatment is photodynamic therapy (PDT), in which an agent (photosensitizer, PS) produces reactive oxygen species (ROS) post-irradiation of cancer cells (containing PS). This study reviews the current discovered potential of PDT and their combinations in treating metastatic melanoma and discusses the impact of different PDT strategies on this cancer. Based on different studies, we realize that PDT at different strategies has shown powerful anti-cancer effects on reducing cell viability, metastasis ability, and the induction of apoptosis in different types of melanomas (in vitro and/or in vivo studies). Importantly, promising outcomes have been reported in the reduction of recurrence rate after PDT-treatment. Also, PDT is a manageable therapeutic approach that may offer an additional powerful option for adjuvant therapy of patients with melanoma.

کلیدواژه‌ها

Malignant melanoma؛ Photodynamic therapy؛ Adjuvant therapy؛ Metastasis؛ Apoptosis

مراجع

[1]    Š. Rusňák, L. Hecová, Z. Kasl, M. Sobotová, and L. Hauer, "Therapy of uveal melanoma A Review," Cesk Slov Oftalmol, vol.77, pp. 1-13, 2020.
[2]        K.W. Nassar and A.C. Tan, "In The mutational landscape of mucosal melanoma," Seminars in cancer biology, Elsevier, vol. 61, pp 139-148, April 2020.
[3]    V.W. Rebecca, R. Somasundaram, and M. Herlyn, "Pre-clinical modeling of cutaneous melanoma" Nature communications, vol. 11, pp. 2858(1-9), 2020.
[4]        D. Schadendorf and A. Hauschild, "Melanoma—the run of success continues," Nature reviews Clinical oncology, vol. 11, pp. 75-76, 2014.
[5]        J.M. Elwood and J. Jopson, "Melanoma and sun exposure: an overview of published studies," International journal of cancer, vol. 73, pp.198-203, 1997.
[6]        A. Shukla, V. Mishra, and P. Kesharwani, "Bilosomes in the context of oral immunization: development, challenges and opportunities," Elsevier, vol. 21, pp. 888-899, 2016.
[7]        F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre Jemal, A. Jemal, "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries," Ca Cancer J Clin, vol. 68, pp. 394-424, 2018.
[8]    A Kumar and V Jaitak, "Natural products as multidrug resistance modulators in cancer," Eur. J. Med. Chem. vol.176, pp. 268-291, 2019.
[9]    F.F. Gellrich, M. Schmitz, S. Beissert, and F. Meier, "Anti-PD-1 and novel combinations in the treatment of melanoma—An update," J. Clin Med. vol. 9, pp. 223(1-17), 2020.
[10]        L.M. Davids and B. Kleemann, "Combating melanoma: the use of photodynamic therapy as a novel, adjuvant therapeutic tool," Cancer Treat. Rev, vol. 37, pp. 465-475, 2011.
[11]        A. Y. Bedikian , M. Millward , H. Pehamberger , R. Conry , M. Gore , U. TrefzerAnna, C. Pavlick , R. DeConti , E. M. Hersh , P. Hersey , J. M. Kirkwood, and F. G. Haluska, "Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group," J. Clin. Oncol. vol. 24, pp. 4738-4745, 2006.
[12]        M.R. Middleton , J.J. Grob , N. Aaronson , G. Fierlbeck , W. Tilgen , S. SeiterM. Gore , S. Aamdal , J. Cebon , A. Coates , B. Dreno , M. Henz , D. Schadendorf , A. Kapp , J. Weiss , U. Fraass , P. Statkevich , M. Muller, and N. Thatcher, "Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma," J. Clin. Oncol. vol.18, pp.158-158, 2000.
[13]        H. Gogas, D. Bafaloukos, and A.Y. Bedikian, "The role of taxanes in the treatment of metastatic melanoma," Melanoma research, vol.14, pp. 415-420, 2004.
[14]    S. Singh, A. Numan, N. Agrawal, M.M. Tambuwala, V. Singh, and P. Kesharwani, "Role of immune checkpoint inhibitors in the revolutionization of advanced melanoma care," Int. Immunopharmacol, vol. 83, pp. 106417, 2020.
[15]        S. Li, F. Zhang, Y. Yu, and Q. Zhang "A dermatan sulfate-functionalized biomimetic nanocarrier for melanoma targeted chemotherapy," Carbohydr. Polym, vol. 235, pp. 115983, 2020.
[16]        Z. Ma, L. Xu, D. Liu, X. Zhang, S. Di, W. Li, J. Zhang, R. J. Reiter, J. Han, X. Li, and  X. Yan, "Utilizing melatonin to alleviate side effects of chemotherapy: a potentially good partner for treating cancer with ageing," Oxid Med Cell Longev. vol.2020, pp. 6841581(1-20), 2020.
[17]    E. Chajon, J. Castelli, H. Marsiglia, and R.  Crevoisier,"The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership," Crit. Rev. Oncol. vol.111, pp. 124-132, 2017.
[18]    C. Robert, J. J. Grob, D. Stroyakovskiy, B. Karaszewska, A. Hauschild, E. Levchenko, V. Chiarion Sileni, J. Schachter, C. Garbe, I. Bondarenko, H. Gogas, M. Mandalá, J. B.A.G. Haanen, C. Lebbé, A. MacKiewicz, P. Rutkowski, P. D. Nathan, A. Ribas, M. A. Davies, K. T. Flaherty,P. Burgess, M. Tan, E. Gasal, M. Voi, D. Schadendorf, and G. V. Long, "Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma," N. Engl. J. Med,  vol. 381, pp. 626-636, 2019.
[19]    M.T. Ballo and K.K. Ang, "Radiation therapy for malignant melanom," vol.  83, pp. 323-342, 2003.
[20]    Sh. Agrawal, J. M. Kane, B. A. Guadagnolo, W. G. Kraybill, and M. T. Ballo, "The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high‐risk, lymph node‐metastatic melanoma," vol. 115, pp. 5836-5844, 2009.
[21]    P. Strojan, B. Jančar, M. Čemažar, M.P. Perme, and M. Hočevar, "Melanoma metastases to the neck nodes: role of adjuvant irradiation," vol. 77, pp. 1039-1045, 2010.
[22]    B. H. Burmeister, M. A. Henderson, J. Ainslie, R. Fisher, J. Di Iulio, B. M. Smithers, A. Hong, K. Shannon, R. A. Scolyer, S. Carruthers, B. J. Coventry, S. Babington, J. Duprat, H. J. Hoekstra, and J. F. Thompson,"Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial," vol. 13, pp. 589-597, 2012.
[23]    
[24]    R. Fuentes, D. Osorio, J. E. Hernandez, D. Simancas-Racines, M. J. Martinez-Zapata, and X. B. Cosp, "Surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis," vol. 20, pp. 12086 (1-44), 2018.
[25]    S. A. Rosenberg, M. T. Lotze, J. C. Yang, S. L. Topalian, A. E. Chang, D. J. Schwartzentruber, P. Aebersold, S. Leitman, W. Marston Linehan, C. A. Seipp, D. E. White, and S. M. Steinberg, "Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer," vol. 85, pp. 622-632, 1993.
[26]    S. S. Agarwala, J. Glaspy, S. J. O'Day, M. Mitchell, J. Gutheil, E. Whitman, R. Gonzalez, E. Hersh, L. Feun, R. Belt, F. Meyskens, K. Hellstrand, D. Wood, J. M. Kirkwood, K. R. Gehlsen, and P. Naredi, "Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma," vol. 20, pp. 125-133, 2002.
[27]    B.T. Fife and J.A. Bluestone, "Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways," vol. 224, pp.166-182, 2008.
[28]    
[29]    R. Marconcini, F. Spagnolo, L. Stefania Stucci, S. Ribero, E. Marra, F. De Rosa, V. Picasso, L.D. Guardo, C. Cimminiello, S. Cavalieri, L. Orgiano, E. Tanda, L. Spano, A. Falcone, and P. Queirolo, "Current status and perspectives in immunotherapy for metastatic melanoma," vol. 9, pp. 12452-12470, 2018.
[30]    P. Ghalioungui, The Ebers papyrus: A new English translation, commentaries and glossaries, Academy of Scientific Research & Technology: 1987.
[31]    O. Raab and Z. biol. "Uber die wirkung fluorescirender stoffe auf infusorien," vol. 39, pp. 524-546, 1900.
[32]    T. J. Dougherty, J. E. Kaufman, A. Goldfarb, K. R. Weishaupt, D. Boyle, and A. Mittleman "Mittleman, A. J. C. r., Photoradiation therapy for the treatment of malignant tumors," vol. 38, pp. 2628-2635, 1978.
[33]    J.M. Dąbrowski and L.G. Arnaut, "Photodynamic therapy (PDT) of cancer: from local to systemic treatment," Photochemical & Photobiological Sciences, vol.14, pp. 1765-1780, 2015.
[34]    B. Chen, B.W. Pogue, P.J. Hoopes, and T. Hasan,  "Vascular and cellular targeting for photodynamic therapy,"     Crit. Rev. Eukaryot. Gene Expr. vol. 16, pp. 279-305, 2016.
[35]    M. Klausen, M. Ucuncu, and M. Bradley, "Design of Photosensitizing Agents for Targeted Antimicrobial Photodynamic Therapy," Molecules, vol. 25, pp. 5239 (1-30), 2020.
[36]    X Zhao, J Liu, J Fan, H Chao, and X Peng, "Recent progress in photosensitizers for overcoming the challenges of photodynamic therapy: from molecular design to application," Chem Soc Rev, vol. 50, pp. 4185-4219, 2021.
[37]    P. Agostinis, K. Berg, K. A. Cengel, Th. H. Foster, A. W. Girotti, S. O. Gollnick, S. M. Hahn, M. R. Hamblin, A. Juzeniene, D. Kessel, M. Korbelik, J. Moan, P. Mroz, D. Nowis, J. Piette, B. C. Wilson, and J. Gola, "Photodynamic therapy of cancer: an update," CA: Cancer J. Clin, vol. 61, pp. 250-281, 2011.
[38]    R. R. Allison, G. H. Downie, R. Cuenca, X.-H. Hu, C. J.h. Childs, and C. H. Sibata, "Photosensitizers in clinical PDT,"     Photodiagnosis Photodyn. Ther.  vol. 1, pp. 27-42, 2004.
[39]    M.R. Detty, S.L. Gibson, and S.J. Wagner, "Current clinical and preclinical photosensitizers for use in photodynamic therapy," J. Med. Chem. vol. 47, pp. 3897-3915, 2004.
[40]        A. Brandis, O. Mazor, E. Neumark, V. Rosenbach-Belkin, Y. Salomon, and A. Scherz, "photobiology, Novel Water‐soluble Bacteriochlorophyll Derivatives for Vascular‐targeted Photodynamic Therapy: Synthesis, Solubility, Phototoxicity and the Effect of Serum Proteins," J. Photochem. Photobiol, vol. 81, pp. 983-992, 2005.
[41]    O. Mazor, A. Brandis, V. Plaks, E. Neumark, V. Rosenbach-Belkin, Y. Salomon, and A. Scherz, "A Novel Water‐soluble Bacteriochlorophyll Derivative; Cellular Uptake, Pharmacokinetics, Biodistribution and Vascular‐targeted Photodynamic Activity Using Melanoma Tumors as a Model," J. Photochem. Photobiol, vol. 81, pp. 342-351, 2005.
[42]    L. G. Arnaut, M. M. Pereira, J. M. Dąbrowski, E. F. F. Silva, F. A. Schaberle, A. R. Abreu, L. B. Rocha, M. M. Barsan, K. Urbańska, G. Stochel, and Ch. M. A. Brett, "Photodynamic therapy efficacy enhanced by dynamics: the role of charge transfer and photostability in the selection of photosensitizers," Chemistry, vol. 20, pp. 5346-5357, 2014.
[43]    L. L. Santos, O. Júlio, M. Eurico, S. Juliana, and S. Cristina, "Treatment of head and neck cancer with photodynamic therapy with redaporfin: a clinical case report," Case Rep Oncol. vol. 11, pp.769-776, 2018.
[44]    T.S. Mang, "Lasers and light sources for PDT: past, present and future," Elsevier, vol. 1, pp. 43-48, 2004.
[45]    J. Jankun, R. W. Keck, E. Skrzypczak-Jankun, L. Lilge, and S. H. Selman, "Diverse optical characteristic of the prostate and light delivery system: implications for computer modelling of prostatic photodynamic therapy," BJU Int.  vol. 95, pp. 1237-1244, 2005.
[46]    B.W. Henderson and Th. J. Dougherty, "photobiology, How does photodynamic therapy work?" Photochem. Photobiol, vol.55, pp. 145-157, 1992.
[47]    Th. J. Dougherty, Ch. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, and Q. Peng, "Photodynamic therapy," J Natl Cancer Inst, vol. 90, pp. 889-905, 1998.
[48]    Á. Juarranz, P. Jaén, F. Sanz-Rodríguez, J. Cuevas, and S. González,  "Photodynamic therapy of cancer. Basic principles and applications," clinical and translational oncology, vol. 10, pp.148-154, 2008.
[49]    B. Ortel, C.R. Shea, and P. Calzavara-Pinton, "Molecular mechanisms of photodynamic therapy," Front Biosci, vol.14, pp. 4157-4172, 2009.
[50]    C. Wellbrock, C. Weisser, E. Geissinger, J. Troppmair, and M. Schartl, "Activation of p59Fyn leads to melanocyte dedifferentiation by influencing MKP-1-regulated mitogen-activated protein kinase signaling," J Biol Chem. vol. 277, pp. 6443-6454, 2002.
[51]    C. Cohen, A. Zavala-Pompa, J. H. Sequeira, M. Shoji, D.G. Sexton, G. Cotsonis, F. Cerimele, B. Govindarajan, N. Macaron and J. L. Arbiser, "Mitogen-actived protein kinase activation is an early event in melanoma progression," Clin Cancer Res. vol. 8, pp. 3728-3733, 2002.
[52]    H. Tsao, G. Yang, V. Goel, H. Wu, and F.G. Haluska, "Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma," J Invest Dermatol. vol.122, pp. 337-341, 2004.
[53]    V. C. Gray-Schopfer, S. d. Rocha Dias, and R. Marais, "The role of B-RAF in melanoma," Cancer Metastasis Rev. vol. 24, pp. 165-183, 2005.
[54]    M. A. Doustvandi, F. Mohammadnejad, B. Mansoori, A. Mohammadi, F. Navaeipour, B. Baradaran, and H. Tajalli, "The interaction between the light source dose and caspase-dependent and-independent apoptosis in human SK-MEL-3 skin cancer cells following photodynamic therapy with zinc phthalocyanine: A comparative study," J Photochem Photobiol B. vol. 176, pp. 62-68, 2017.
[55]    Z. Pan, J. Fan, Q. Xie, X. Zhang, W. Zhang, Q. Ren, M. Li, Q. Zheng, J. Lu, and D. Li, "Pharmacotherapy, Novel sulfonamide porphyrin TBPoS-2OH used in photodynamic therapy for malignant melanoma," Biomed. Pharmacother, vol. 133, pp. 111042 (1-11), 2021.
[56]    W. Szlasa, S. Supplitt, M. Drąg-Zalesińska, D. Przystupski, K. Kotowski, A. Szewczyk, P. Kasperkiewicz, J. Saczko, and J. Kulbacka, "Pharmacotherapy, Effects of curcumin based PDT on the viability and the organization of actin in melanotic (A375) and amelanotic melanoma (C32)–in vitro studies," Biomed Pharmacother. vol. 132, pp. 110883 (1-12), 2020.
[57]    W. M. Star, H. P. Marijnissen, A. E. van den Berg-Blok, J. A. Versteeg, K. A. Franken, and H. S. Reinhold, "Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers," Cancer Res. vol. 46, pp. 2532-2540, 1986.
[58]    B. Chen, B. W. Pogue, J. M. Luna, R. L. Hardman, P. J. Hoopes, and T. Hasan, "Tumor vascular permeabilization by vascular-targeting photosensitization: effects, mechanism, and therapeutic implications," Clin Cancer Res. vol. 12, pp. 917-923, 2006.
[59]    B. W. Henderson, S. M. Waldow, T. S. Mang, W. R. Potter, P. B. Malone, and T. J. Dougherty, "Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy," Cancer Res . vol. 45, pp. 572-576, 1985.
[60]    V. H. Fingar, P. K. Kik, P. S. Haydon, P. B. Cerrito, M. Tseng, E. Abang and T. J. Wieman,  "Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)," Br J Cancer, vol. 79, pp.1702-1708, 1999.
[61]    P. Nowak-Sliwinska, J. R. van Beijnum, M. van Berkel, H. van den Bergh and A. W. Griffioen,  "Vascular regrowth following photodynamic therapy in the chicken embryo chorioallantoic membrane," Angiogenesis, vol. 13, pp. 281-292, 2010.
[62]    T. Tammela, A. Saaristo, T. Holopainen, S. Ylä-Herttuala, L. C. Andersson, S. Virolainen, I. Immonen, and K. Alitalo,"Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis," Sci Transl Med.  vol. 3, pp. 69-80, 2011.
[63]        J. Zhou, Sh. Geng, W. Ye, Q. Wang, R. Lou , Q. Yin, B. Du, and H. Yao, "ROS-boosted photodynamic therapy against metastatic melanoma by inhibiting the activity of antioxidase and oxygen-producing nano-dopants," Pharmacol Res. vol. 158, pp. 104885, 2020.
[64]    S. V. Sheleg, E. A. Zhavrid, T. V. Khodina, G.A. Kochubeev, Y. P. Istomin, V. N. Chalov, and I. N. Zhuravkin, "photoimmunology; photomedicine, Photodynamic therapy with chlorin e6 for skin metastases of melanoma," Photodermatol. Photoimmunol. Photomed. vol. 20, pp. 21-26, 2004.
[65]    C. Donohoe, M. O. Senge, L. G. Arnaut, and L.C. Gomes-da-Silva, "Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity," Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol. 1872, pp. 188308, 2019.
[66]    N.N. Danial and S.J. Korsmeyer, "Cell death: critical control points," Cell, vol. 116, pp. 205-219, 2004.
[67]    A. Boice and L. Bouchier-Hayes, "Targeting apoptotic caspases in cancer," Biochim Biophys Acta Mol Cell Res, vol. 1867, pp. 118688, 2020.
[68]    C.B. Thompson, "Apoptosis in the pathogenesis and treatment of disease," Science, vol.267, pp. 1456-1462, 1995. 
[69]    D.R. McIlwain, T. Berger, and T.W. Mak, "Caspase functions in cell death and disease," Cold Spring Harb Perspect Biol. vol. 5, pp. a008656 (1-30), 2013.
[70]    D. Hanahan and R.A. Weinberg,  "The hallmarks of cancer," cell, vol. 100, pp. 57-70, 2000.
[71]    S.W. Ryter and C.J. Gomer, "photobiology, Nuclear factor κB binding activity in mouse L1210 cells following Photofrin II‐mediated photosensitization," Photochem. Photobiol. vol. 58, pp. 753-756, 1993.
[72]    D.A. Gewirtz, "Autophagy, senescence and tumor dormancy in cancer therapy," Autophagy, vol. 5, pp. 1232-1234, 2009.
[73]    X. Ge, J. Liu, Z. Shi, L. Jing, N. Yu, X. Zhang, Y. Jiao, Y. Wang, and P. Andy Li, "Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells," European Journal of Dermatology, vol. 26, pp. 164-172, 2016.
[74]    N.L. Oleinick, R.L. Morris, and I. Belichenko, "The role of apoptosis in response to photodynamic therapy: what, where, why, and how," Photochem. Photobiol. vol.1, pp. 1-21, 2002.
[75]    P. Agostinis, E. Buytaert, H. Breyssens, and N. Hendrickx, "Regulatory pathways in photodynamic therapy induced apoptosis," Photochem Photobiol Sci, vol. 3, pp. 721-729, 2004.
[76]        M. A. Doustvandi, F. Mohammadnejad, B. Mansoori, H. Tajalli, A. Mohammadi, A. Mokhtarzadeh, E. Baghbani, V. Khaze, Kh. Hajiasgharzadeh, M. Maleki Moghaddam, M. R Hamblin, and B. Baradaran, "Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells," Photodiagnosis Photodyn Ther. vol. 28, pp. 88-97, 2019.
[77]    E. Buytaert, G. Callewaert, J. R. Vandenheede, and P. Agostinis, "Deficiency in apoptotic effectors Bax and Bak reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum," Autophagy. vol. 2, pp. 238-240, 2006.
[78]    S. Mohamed Ali, S. Kh. Chee, G. Yik Yuen, and M. Olivo, "Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells," Int J Mol Med.  vol. 9, pp. 601-616, 2002.
[79]    J. Cai, Q. Zheng, H. Huang, and B. Li, "5-aminolevulinic acid mediated photodynamic therapy inhibits survival activity and promotes apoptosis of A375 and A431 cells," Photodiagnosis Photodyn Ther. vol. 21, pp. 257-262, 2018.
[80]    J. Nackiewicz, M. Kliber-Jasik, and M. Skonieczna, "Biology, P. B., A novel pro-apoptotic role of zinc octacarboxyphthalocyanine in melanoma me45 cancer cell's photodynamic therapy (PDT)," J. Photochem. Photobiol. vol. 190, pp. 146-153, 2019.
[81]    J. E. Gershenwald, R.A. Scolyer, K. R. Hess, V. K. Sondak, G. V. Long, M. I. Ross, A. J. Lazar, M.B. Faries, J.M. Kirkwood, G. A. McArthur, L. E. Haydu, A.M. M. Eggermont, K.T. Flaherty, C.M. Balch, and J. F. Thompson,  "Melanoma staging: evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual," CA Cancer J Clin. vol. 67, pp. 472-492, 2017.
[82]    S.A. Blankenstein and A.C.J. van Akkooi, "Adjuvant systemic therapy in high-risk melanoma," Melanoma Res. vol. 29, pp. 358-364, 2019.
[83]    A. M. M. Eggermont, Ch. U. Blank, M. Mandala, G. V. Long, V. G. Atkinson, S. Dalle, A. Haydon, M. Lichinitser, A. Khattak, M. S. Carlino, Sh. Sandhu, J. Larkin, S. Puig, P.A. Ascierto, P. Rutkowski, D. Schadendorf, R. Koornstra, L. Hernandez-Aya , A. M. Di Giacomo, A. J. v. den Eertwegh, J.-J. Grob, R. Gutzmer, R. Jamal, P. C. Lorigan, R. Lupinacci, C. Krepler, N. Ibrahim, M. Kicinski, S. Marreaud, A. C. van Akkooi, S. Suciu, and C. Robert, "Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma," Eur J Cancer. vol. 116, pp.148-157, 2019.    
[84]    Y.-Y. Huang, D. Vecchio, P. Avci, R. Yin, M. Garcia-Diaz, and M.R. Hamblin, "Melanoma resistance to photodynamic therapy: new insights," Biol Chem. vol. 394, pp. 239 (1-22), 2013.
[85]    F.N. Biteghe and L.M. Davids "A combination of photodynamic therapy and chemotherapy displays a differential cytotoxic effect on human metastatic melanoma cells," J Photochem Photobiol B. vol. 166, pp.18-27, 2017.
[86]    J. Tang, H. Zhou, X. Hou, L. Wang, Y. Li, Y. Pang, Ch. Chen, G. Jiang, and Y. Liu, "Enhanced anti-tumor efficacy of temozolomide-loaded carboxylated poly (amido-amine) combined with photothermal/photodynamic therapy for melanoma treatment," Cancer Lett.  vol. 423, pp. 16-26, 2018.
[87]    P.J. Farmer, Sh. Gidanian, B. Shahandeh, A. J. D. Bilio, N. Tohidian, and F. L. Meyskens Jr "Melanin as a target for melanoma chemotherapy: pro‐oxidant effect of oxygen and metals on melanoma viability," Pigment Cell Res. vol. 16, pp. 273-279, 2003.    
[88]    K. G. Chen, R. D. Leapman, G. Zhang, B. Lai, J. C. Valencia, C. O. Cardarelli, W. D. Vieira, V.J. Hearing, and M. M. Gottesman,"Influence of melanosome dynamics on melanoma drug sensitivity," J Natl Cancer Inst. vol. 101, pp. 1259-1271, 2009.
[89]    G. Raposo and M.S. Marks,  "The dark side of lysosome‐related organelles: specialization of the endocytic pathway for melanosome biogenesis," Traffic, vol. 3, pp. 237-248, 2002.
[90]    V.J. Hearing, "Biogenesis of pigment granules: a sensitive way to regulate melanocyte function," J. Dermatol. Sci, vol. 37, pp. 3-14, 2005.
[91]    Q. Chen, H. Dan, F. Tang, J. Wang, X. Li, J. Cheng, H. Zhao, and X. Zeng,"Photodynamic therapy guidelines for the management of oral leucoplakia," Int J Oral Sci. vol. 11, pp. 1-5, 2019.
[92]    J.J. Hu, Q. Lei, and X.Z. Zhang, "Recent advances in photonanomedicines for enhanced cancer photodynamic therapy," Prog. Mater. Sci, vol.114, pp. 100685, 2020.