Melanin content in melanoma metastases affects the outcome of radiotherapy

Abstract

Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma.

MAPK Pathway Inhibitors Sensitize BRAF-Mutant Melanoma to an Antibody-Drug Conjugate Targeting GPNMB

“…6). This hypothesis is supported by the observation that patients with pigmented melanoma experience shorter survival times than those with amelanotic melanoma following exposure to oxidizing radiotherapy (48). …”

Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases

“…The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on previous cell-based and clinical research, it could suggest that inhibition of melanogenesis can improve radiotherapy modalities [42, 43]. The active melanogenesis could not only impair the cytotoxic action of cyclophosphamid but also has potent immunosuppressive properties.…”

Effects of Ganodermanondiol, a New Melanogenesis Inhibitor from the Medicinal Mushroom Ganoderma lucidum

“…Likewise, although further studies are required to elucidate an anti-melanogenic effect of ganodermanondiol in human melanocytes, this compound warrants further investigation for development as a potential ingredient in cosmetic applications. Furthermore, several reports suggest that the inhibition of melanogenesis might represent a valid therapeutic target for the treatment of melanotic melanomas [6,55,56,57]. Thus, ganodermanondiol may also be a potentially useful therapeutic agent for the management of melanoma.…”