Current and Future Roles of Targeted Therapy and Immunotherapy in Advanced Melanoma

Abstract

Skin cancer is the most common form of cancer in the United States.1 Most patients develop nonmelanoma skin cancer, where surgical excision of the primary lesion remains effective for early disease, and survival rate is high. Although melanoma accounts for less than 5% of cases of skin cancer, it accounts for most (75%) skin cancer-related deaths. It is estimated that, in 2014, almost 76,100 men and women in the United States will be diagnosed with invasive melanoma of the skin, and close to 9,710 people will die from the disease. Furthermore, melanoma is the most common form of cancer for young adults aged 25 to 29 years and the second most common form of cancer for young people aged 15 to 29 years.2 Given the prevalence of melanoma in young individuals, it accounts for 1 of the 10 leading causes of years of life lost. 3 The overall 5-year survival rate from diagnosis for patients whose melanoma is detected early, before the tumor has spread to regional lymph nodes or other organs, is about 98% in the United States, falling to 62% when the disease reaches

Bone marrow metastasis of malignant melanoma in childhood arising within a congenital melanocytic nevus

“…apart from cytokines, monoclonal antibodies and dendritic cell vaccines, targeted "immune checkpoint blockade" therapy including inhibitors of cytotoxic T-lymphocyte antigen 4 (cTla-4) (ipilimumab, tremelimumab), mitogen-activated protein kinase (mapK) pathway inhibitors (vemurafenib, cobimetinib, dabrafenib and trametinib) and new immunotherapeutic agents such as programmed cell death 1 (pd-1) receptor and its ligand (pd-l1) blocking antibodies (nivolumab, pembrolizumab) have been introduced, igniting a revolution in the treatment of malignant melanoma since the Fda's approval of anti-cTla-4 therapy in 2011 (ref. [18][19][20][21] ). although combined inhibition (e.g.…”

“…laminectomy of l5 and s1 with subtotal resection of a spinal metastasis was required six weeks later due to a neurological impairment including paraparesis and leg pain. after four applications of ipilimumab, active treatment was stopped because of tumor progression and rapid clinical deterioration (anorexia, severe cachexia and poor performance status -lansky score [10][11][12][13][14][15][16][17][18][19][20]. at the parents' request, the therapy was continued with palliative metronomic chemotherapy (vinblastine weekly) plus symptomatic treatment.…”

The Polysaccharide Extracted from <i>Umbilicaria esculenta</i> Inhibits Proliferation of Melanoma Cells through ROS-Activated Mitochondrial Apoptosis Pathway

“…3,4) The emergence of targeted therapy such as BRAF and mitogen-activated protein extracellular kinase (MEK) inhibitors, and immune checkpoint blockade such as anti-CTLA-4 and anti-PD-1 monoclonal antibodies marked great breakthrough in the management of patients with advanced melanoma. 5,6) However, it is also not satisfied that, although these small targeted molecules have been proved to improve patients' QOL to some extent, adverse events such as pyrexia, photosensitivity and secondary cutaneous squamous-cell carcinomas and drug resistance which developed in about half of patients within several months treatment limited their effects. [7][8][9] Due to the characteristics of good efficacy, safety, and less toxicity to normal body tissues and organs, the natural medicine have attracted growing attention.…”

Time and tumor type (primary or metastatic) do not influence the detection of BRAF/NRAS mutations in formalin fixed paraffin embedded samples from melanomas

“…Although a non-significant decreased percentage of samples with both genes correctly sequenced was observed, we could obtain the sequencing results of NRAS and BRAF in more than 60% of samples kept for more than 10 years in FFPE blocks. The optimization of the sequencing process, the existing drug combinations and the development of new drugs will play an important role in the future of melanoma therapy [28]. Some strategies have been developed to cryopreserve melanoma samples in bio-banking with wellestablished mapping protocols using imaging techniques [29], but these types of strategies are not common.…”