benign tumors are usually not called melanomas anymore and the word melanoma is now usually taken to mean malignant melanoma unless otherwise specified. terms such as "benign melanocytic tumor" unequivocally label the benign types, and modern histopathologic tumor classifications used in medicine do not use the word for benign tumors. research pharmacotherapy research for un-resectable or metastatic malignant melanoma is ongoing. targeted therapies in clinical research, adoptive cell therapy and gene therapy, are being tested. two kinds of experimental treatments developed at the national cancer institute (nci), have been used in metastatic melanoma with tentative success. the first treatment involves adoptive cell therapy (act) using tils immune cells (tumor-infiltrating lymphocytes) isolated from a person's own melanoma tumor. these cells are grown in large numbers in a laboratory and returned to the patient after a treatment that temporarily reduces normal t cells in the patient's body. til therapy following lymphodepletion can result in durable complete response in a variety of setups. the second treatment, adoptive transfer of genetically altered autologous lymphocytes, depends on delivering genes that encode so called t cell receptors (tcrs), into patient's lymphocytes. after that manipulation lymphocytes recognize and bind to certain molecules found on the surface of melanoma cells and kill them. a cancer vaccine showed modest benefit in late-stage testing in 2009 against melanoma. braf inhibitors about 60% of melanomas contain a mutation in the b-raf gene. early clinical trials suggested that b-raf inhibitors including plexxicon's vemurafenib could lead to substantial tumor regression in a majority of patients if their tumor contain the b-raf mutation. in june 2011, a large clinical trial confirmed the positive findings from those earlier trials. in august 2011, vemurafenib received fda approval for the treatment of late-stage melanoma. in may 2013 the us fda approved dabrafenib as a single agent treatment for patients with braf v600e mutation-positive advanced melanoma. some researchers believe that combination therapies that simultaneously block multiple pathways may improve efficacy by making it more difficult for the tumor cells to mutate before being destroyed. in october 2012 a study reported that combining dabrafenib with a mek inhibitor trametinib led to even better outcomes. compared to dabrafenib alone, progression-free survival was increased to 41% from 9%, and the median progression-free survival increased to 9.4 months versus 5.8 months. some side effects were, however, increased in the combined study. in january 2014, the fda approved the combination of dabrafenib and trametinib for the treatment of people with braf v600e/k-mutant metastatic melanoma. in june 2018, the fda approved the combination of a braf inhibitor encorafenib and a mek inhibitor binimetinib for the treatment of un-resectable or metastatic melanoma with a braf v600e or v600k mutation. eventual resistance to braf and mek inhibitors may be due to a cell surface protein known as epha2 which is now being investigated. ipilimumab at the american society of clinical oncology conference in june 2010, the bristol-myers squibb pharmaceutical company reported the clinical findings of their drug ipilimumab. the study found an increase in median survival from 6.4 to 10 months in patients with advanced melanomas treated with the monoclonal ipilimumab, versus an experimental vaccine. it also found a one-year survival rate of 25% in the control group using the vaccine, 44% in the vaccine and ipilimumab group, and 46% in the group treated with ipilimumab alone. however, some have raised concerns about this study for its use of the unconventional control arm, rather than comparing the drug against a placebo or standard treatment. the criticism was that although ipilimumab performed better than the vaccine, the vaccine has not been tested before and may be causing toxicity, making the drug appear better by comparison. ipilimumab was approved by the fda in march 2011 to treat patients with late-stage melanoma that has spread or cannot be removed by surgery. in june 2011, a clinical trial of ipilimumab plus dacarbazine combined this immune system booster with the standard chemotherapy drug that targets cell division. it showed an increase in median survival for these late stage patients to 11 months instead of the 9 months normally seen. researchers were also hopeful of improving the five year survival rate, though serious adverse side-effects were seen in some patients. a course of treatment costs $120,000. the drug's brandname is yervoy. surveillance methods advances in high resolution ultrasound scanning have enabled surveillance of metastatic burden to the sentinel lymph nodes. the screening and surveillance of ultrasound in melanoma trial (sunmel) is evaluating ultrasound as an alternative to invasive surgical methods. oncolytic virotherapy in some countries oncolytic virotherapy methods are studied and used to treat melanoma. oncolytic virotherapy is a promising branch of virotherapy, where oncolytic viruses are used to treat diseases; viruses can increase metabolism, reduce anti-tumor immunity and disorganize vasculature. talimogene laherparepvec (t-vec) (which is a herpes simplex virus type 1–derived oncolytic immunotherapy), was shown to be useful against metastatic melanoma in 2015 with an increased survival of 4.4 months. notes incidence is in comparison to all melanomas. a pathological n category is not required for t1 melanomas. in such cases, clinical n information may be used.