Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion

Objectives

Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone.

黑色素瘤的治疗新进展

黑色素瘤的遗传学特性颇具代表性,常作为肿瘤研究的首选。本文对黑色素瘤发病的分子机理研究与基因治疗新进展作综述。     

黑色素瘤的靶向治疗

黑色素瘤是常见的皮肤肿瘤,它放化疗的效果差,达卡巴嗪仍是目前晚期黑色素瘤化疗药物治疗中公认的金标准,但有效率仅8%~12%左右。现抗细胞毒T淋巴细胞相关抗原4(cytotoxic Tlymphocyte-associated antigen-4,CTLA-4)单抗和针对基因突变的分子靶向药物的出现,增加了治疗的手段并取得了好的疗效。这些药物在延长晚期黑色素瘤患者的生存期方面取得了令人瞩目的突破,有可能对晚期黑色素瘤患者的治疗进行彻底的革命,这为治疗晚期恶性黑色素瘤患者带来希望,在目前常用的药物中,虽然威罗菲尼和易普利姆玛被用来治疗转移性黑色素瘤,但他们都有局限性。威罗菲尼有效应答时间短,而易普利姆玛应答率低。本文就恶性黑色素瘤分子靶向治疗的研究进展进行综述,未来几年靶向药物的联合治疗及新的有效靶点的发现可能会成为黑色素瘤治疗的突破点。     

Focus: Personalized Medicine: Tailoring the Treatment of Melanoma: Implications for Personalized Medicine

Oncology has been revolutionized by the ability to selectively inhibit the growth of cancerous cells while ostensibly avoiding the disruption of proteins and pathways necessary for normal cellular function. This paradigm has triggered an explosion of targeted therapies for cancer, creating a burgeoning billion-dollar industry of small molecules and monoclonal antibodies [1]. Largely due to these new treatments, spending on cancer pharmaceuticals has surpassed $100 billion worldwide [2]. In particular, the treatment of melanoma, a deadly and fast-spreading form of skin cancer, has been transformed by these new targeted therapies. In this mini-review, we summarize the progress made in the field of personalized treatment of melanoma, with an emphasis on targeted therapies. We then outline future directions for treatment, including novel cell-mediated therapies and new potential targets.     

Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution

Targeted internal radionuclide therapy (TRT) could be an efficient, specific way to treat disseminated melanoma. Based on a previous pharmacomodulation study, we selected a quinoxaline-derived molecule (ICF01012) for its melanin specificity and kinetic properties suitable for TRT. Here, we determined the efficacy of [¹³¹I]ICF01012 radiotherapy in vitro and in vivo in relation to melanogenesis using human melanoma models. [¹²⁵I]ICF01012 uptake was first assessed in relation to melanin content. We found that melanin distribution in different models was representative of pathology seen in human tumours: melanin content was high in the extracellular space of SKMel3 tumours, and accumulated primarily in melanophages in M4Beu tumours. Targeted [¹³¹I]ICF01012 radiotherapy had a strong anti-tumoural efficacy in pigmented versus unpigmented tumours, regardless of target distribution and content. This study supports the use of melanin targeting with ¹³¹I-labelled iodoquinoxaline for effective treatment of melanoma.     

Effective inhibition of melanoma by BI-69A11 is mediated by dual targeting of the AKT and NF-κB pathways

In melanoma, the activation of pro-survival signaling pathways, such as the AKT and NF-κB pathways, is critical for tumor growth. We have recently reported that the AKT inhibitor BI-69A11 causes efficient inhibition of melanoma growth. Here, we show that in addition to its AKT inhibitory activity, BI-69A11 also targets the NF-κB pathway. In melanoma cell lines, BI-69A11 inhibited TNF-α-stimulated IKKα/β and IκB phosphorylation as well as NF-κB reporter gene expression. Furthermore, the effective inhibition of melanoma growth by BI-69A11 was attenuated upon NF-κB activation. Mechanistically, reduced NF-κB signaling by BI-69-A11 is mediated by the inhibition of sphingosine kinase 1, identified in a screen of 315 kinases. Significantly, we demonstrate that BI-69A11 is well tolerated and orally active against UACC 903 and SW1 melanoma xenografts. Our results demonstrate that BI-69A11 inhibits both the AKT and the NF-κB pathways and that the dual targeting of these pathways may be efficacious as a therapeutic strategy in melanoma.