A Review of Advanced Cutaneous Melanoma Therapies and Their Mechanisms, from Immunotherapies to Lysine Histone Methyl Transferase Inhibitors.

Advanced cutaneous melanoma is considered to be the most aggressive type of skin cancer and has variable rates of treatment response. Currently, there are some classes of immunotherapy and target therapies for its treatment. Immunotherapy can inhibit tumor growth and its recurrence by triggering the host's immune system, whereas targeted therapy inhibits specific molecules or signaling pathways. However, melanoma responses to these treatments are highly heterogeneous, and patients can develop resistance. Epigenomics (DNA/histone modifications) contribute to cancer initiation and progression. Epigenetic alterations are divided into four levels of gene expression regulation: DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation. Deregulation of lysine methyltransferase enzymes is associated with tumor initiation, invasion, development of metastases, changes in the immune microenvironment, and drug resistance. The study of lysine histone methyltransferase (KMT) and nicotinamide N-methyltransferase (NNMT) inhibitors is important for understanding cancer epigenetic mechanisms and biological processes. In addition to immunotherapy and target therapy, the research and development of KMT and NNMT inhibitors is ongoing. Many studies are exploring the therapeutic implications and possible side effects of these compounds, in addition to their adjuvant potential to the approved current therapies. Importantly, as with any drug development, safety, efficacy, and specificity are crucial considerations when developing methyltransferase inhibitors for clinical applications. Thus, this review article presents the recently available therapies and those in development for advanced cutaneous melanoma therapy.

Sentinel node biopsy should not be recommended for patients with thick melanoma.

OBJECTIVE: To ascertain whether there is any relationship between the state of the sentinel lymph node histopathology, recurrence and mortality from thick melanoma in patients undergoing SLNB over a long follow-up. METHODS: Eighty-six patients with thick melanoma undergoing SLNB were selected from a prospective database. Lymphoscintigraphy, lymphatic mapping and intraoperative gamma probe detection were performed in all patients. The sentinel lymph node (SLN) was analyzed by HE and immunohistochemistry. Complete lymphadenectomy was indicated for patients with positive sentinel node. The histopathological SLN status was related to the rate of recurrence and mortality from melanoma. RESULTS: One hundred and sixty-six SLNs were taken from the 86 patients. Ages ranged from 18 to 73 years. There were 47 women and 39 men. Micrometastases were found in 44 patients. Forty-two patients underwent complete lymphadenectomy. Seven other patients had positive lymph node. Among the 44 patients with positive sentinel node, there were 20 recurrences and 15 deaths. There were 18 recurrences and 12 deaths in the group with negative SLN. The Breslow thickness was not correlated with the histopathological SLN status. The histopathological SLN status did not affect the rates of recurrence and mortality (Fisher test, p = 1.00). The median follow-up was 69 months. CONCLUSION: Considering the lack of evidence of benefit, SLNB should not be indicated for patients with thick melanoma outside of clinical studies.

[Brazilian gamma detection device for sentinel lymph node biopsy]. / Equipamento brasileiro de detecção gama intra-operatória para biópsia de linfonodo sentinela.

OBJECTIVE: To test the effectiveness of an intra-operative gamma detection Brazilian device (IPEN) on sentinel lymph node biopsy (SLNB) procedures. METHODS: Forty melanoma or breast cancer patients with indication for undergoing SLNB were studied. Lymphoscintigraphy was done 2 to 24 hours prior to surgery. Lymphatic mapping with vital dye and gamma detection were performed intraoperatively. For gamma detection Neoprobe 1500 was used followed by IPEN (equipment under test) in the first 20 patients and for the remaining half IPEN was used first to verify its ability to locate the sentinel node (SN). Measurements were taken from the radiopharmaceutical product injection site, from SN (in vivo and ex vivo) and from background. It was recorded if the SN was stained or not and if it was found easily by surgeon. RESULTS: There were 33 (82.5%) breast cancer and 7 (17.5%) melanoma patients. Ages varied from 21 to 68 year-old (median age of 46). Sex distribution was 35 (87.5%) women and 5 (12.5%) men. Sentinel node was found in all but one patient. There was no statistical difference between the reasons ex vivo/ background obtained with the measures of both equipments (p=0, 2583-ns). The SN was easily found by the surgeon with both devices. CONCLUSION: The SLNB was successfully performed using either equipment. It was possible to do SLNB with the Brazilian device developed by IPEN without prejudice for the patient.