Melanoma resistance to photodynamic therapy: new insights.

Melanoma resistance to photodynamic therapy: new insights.
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DOI:
10.1515/hsz-2012-0228
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发表时间:
2013-02
影响因子:
3.7
通讯作者:
Hamblin MR
Hamblin MR
中科院分区:
生物学2区
文献类型:
--
作者:
Huang YY;Vecchio D;Avci P;Yin R;Garcia-Diaz M;Hamblin MR

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黑色素瘤是最危险的皮肤癌,发病率急剧上升,晚期预后较差。尽管 BRAF 抑制剂等现代靶向疗法显示出一些希望,但黑色素瘤对传统化疗和放疗具有高度耐药性。光动力疗法(PDT,光敏染料和可见光的组合)已针对黑色素瘤进行了测试,并取得了一些有希望的结果,但黑色素瘤通常被认为对 PDT 也具有抵抗力。高色素黑色素的光学干扰、黑色素的抗氧化作用、黑素体内光敏剂的隔离、细胞凋亡途径的缺陷以及 ATP 结合盒 (ABC) 转运蛋白的光敏剂外流都与黑色素瘤对 PDT 的抵抗有关。克服黑色素瘤对 PDT 耐药性的方法包括: 发现在 700-800 nm 近红外光谱区域吸收的高活性光敏剂;可以暂时减少黑色素数量或色素沉着的干预措施;可以逆转细胞凋亡缺陷或抑制光敏剂药物流出的化合物;免疫治疗方法可以利用 PDT 的能力来激活宿主免疫系统对所治疗肿瘤的作用。
Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor.
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