Abstract
Melanoma is the deadliest type of skin cancer, due to its invasiveness and limited treatment efficacy. The main therapy for primary melanoma and solitary organ metastases is wide excision. Adjuvant therapy, such as chemotherapy and targeted therapies are mainly used for disseminated disease. Radiotherapy (RT) is a powerful treatment option used in more than 50% of cancer patients, however, conventional RT alone is unable to eradicate melanoma. Its general radioresistance is attributed to overexpression of repair genes in combination with cascades of biochemical repair mechanisms. A novel sophisticated technique based on synchrotron-generated, spatially fractionated RT, called Microbeam Radiation Therapy (MRT), has been shown to overcome these treatment limitations by allowing increased dose delivery. With MRT, a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose microbeams that are tens of micrometres wide and spaced a few hundred micrometres apart. Different preclinical models demonstrated that MRT has the potential to completely ablate tumours, or significantly improve tumour control while dramatically reducing normal tissue toxicity. Here, we discuss the role of conventional RT-induced immunity and the potential for MRT to enhance local and systemic anti-tumour immune responses. Comparative gene expression analysis from preclinical tumour models indicated a specific gene signature for an ‘MRT-induced immune effect’. This focused review highlights the potential of MRT to overcome the inherent radioresistance of melanoma which could be further enhanced for future clinical use with combined treatment strategies, in particular, immunotherapy.
Highlights
Introduction to MelanomaMelanoma is a highly malignant type of skin cancer that develops from melanocytes, the cells that produce the UV-absorbing pigment melanin
Another explanation was provided by Wu et al [18], who analysed the response of the metabolome following ionizing radiation (IR) in mouse B16 melanoma cells
IR is a type of sterile tissue injury, and IR-induced inflammation differs from the infectious inflammatory response, it is still a part of a basic immunological process; a protective response that aims to eliminate the cause of injury, remove damaged cells, and repair tissues
Summary
Melanoma is a highly malignant type of skin cancer that develops from melanocytes, the cells that produce the UV-absorbing pigment melanin. To treat local or satellite metastases, surgical excision of the primary tumour and of metastases (in lymph nodes or distant organs) should always be performed whenever possible with curative intent. In macroscopic nodal disease, complete lymph node dissection remains the key strategy [12,13]. Adjuvant therapy, such as chemotherapy and targeted therapies (e.g., inhibition of BRAF and c-KIT), are employed for the treatment of melanoma. The results of this analysis reveal a specific gene signature for an ‘MRT-induced immune effect’. We share our own experience about the successful treatment of mouse B16-F10 melanoma with MRT
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