摘要
背景:恶性黑色素瘤是最具侵袭性的恶性肿瘤之一,具有不可预测的进化。尽管有许多治疗选择,如化疗、BRAF抑制剂和免疫治疗,但晚期黑色素瘤预后仍然严重。光动力疗法(PDT)已成功应用于肺、食管、膀胱、非黑色素瘤皮肤和头颈部癌症的一线或姑息疗法。然而,传统的PDT显示出一些缺点,限制了其在黑色素瘤中的临床应用。 目的:最重要的挑战是克服黑色素瘤抵抗,由于黑色素体的捕获、黑色素的存在、氧化应激防御的增强、凋亡途径的缺陷、免疫逃避、新生血管的刺激。 方法:本文认为:(1)黑色素瘤中释放的主要信号分子途径是个性化治疗的潜在靶点,包括PDT;(2)黑色素瘤PDT的临床研究结果,特别是晚期转移期;(3)抗黑色素瘤光敏剂的设计进展;(4)抑制肿瘤新生血管形成,以及(5)衍生疗法的优点,如光热疗法、超声动力学疗法。 结果:PDT具有微创性和低副作用,是治疗晚期黑色素瘤的一种有希望的替代疗法。高效的黑色素瘤PDT需要:(1)改良的肿瘤靶向性NIR吸收光敏剂,能够在肿瘤和血管系统细胞内诱导大量不同的活性氧,可能允许治疗方法;(2)有效的辅助免疫疗法。 结论:PDT与免疫刺激相结合可能是克服黑色素瘤耐药性,获得更好、可持续的临床效果的关键。
关键词: 光动力疗法,黑色素瘤,光敏剂,新生血管,免疫疗法,氧化应激,信号通路
Current Medicinal Chemistry
Title:Photodynamic Therapy in Melanoma - Where do we Stand?
Volume: 25 Issue: 40
关键词: 光动力疗法,黑色素瘤,光敏剂,新生血管,免疫疗法,氧化应激,信号通路
摘要: Background: Malignant melanoma is one of the most aggressive malignant tumors, with unpredictable evolution. Despite numerous therapeutic options, like chemotherapy, BRAF inhibitors and immunotherapy, advanced melanoma prognosis remains severe. Photodynamic therapy (PDT) has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical PDT has shown some drawbacks that limit its clinical application in melanoma.
Objective: The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation.
Method: In this review we considered: (1) main signaling molecular pathways deregulated in melanoma as potential targets for personalized therapy, including PDT, (2) results of the clinical studies regarding PDT of melanoma, especially advanced metastatic stage, (3) progresses made in the design of anti-melanoma photosensitizers (4) inhibition of tumor neoangiogenesis, as well as (5) advantages of the derived therapies like photothermal therapy, sonodynamic therapy.
Results: PDT represents a promising alternative palliative treatment for advanced melanoma patients, mainly due to its minimal invasive character and low side effects. Efficient melanoma PDT requires: (1) improved, tumor targeted, NIR absorbing photosensitizers, capable of inducing high amounts of different ROS inside tumor and vasculature cells, possibly allowing a theranostic approach; (2) an efficient adjuvant immune therapy.
Conclusion: Combination of PDT with immune stimulation might be the key to overcome the melanoma resistance and to obtain better, sustainable clinical results.
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Cite this article as:
Photodynamic Therapy in Melanoma - Where do we Stand?, Current Medicinal Chemistry 2018; 25 (40) . https://dx.doi.org/10.2174/0929867325666171226115626
DOI https://dx.doi.org/10.2174/0929867325666171226115626 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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