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Malignant Melanoma

»	What is melanoma?
»	How common is malignant melanoma in the United States?
»	What causes melanoma?
»	What groups have a genetic predisposition to familial melanoma?
»	List the risk factors for melanoma.
»	List the high-risk groups for developing melanoma.
»	Do all melanomas develop from atypical nevi?
»	What are cancer stem cells?
»	Is melanoma a single disease?
»	What are the molecular pathways in melanoma?
»	Is there a host immune response to melanoma?
»	Describe the clinical appearance of melanoma.
»	What are the ABCDEs of melanoma?
»	What is dermoscopy?
»	Where on the body does melanoma most commonly arise?
»	Are there different types of melanoma?
»	What are Clark’s levels?
»	What is Breslow’s depth?
»	What other findings should be reported in the histopathologic diagnosis of melanoma?
»	What are the common immunohistochemical (IHC) markers utilized in the diagnosis of melanoma?
»	Are there other factors with prognostic impact in patients with melanoma?
»	How are patients with melanoma evaluated after the initial diagnosis?
»	What is the most current system for staging melanoma?
»	How is melanoma treated?
»	How wide should surgical margins be?
»	What is the most important risk factor for local recurrence of primary melanoma?
»	Does a biopsy of melanoma increase the risk of spreading tumor cells or causing metastases?
»	Describe the recommended follow-up for a patient with melanoma.
»	Which tests or examinations are conducted during the routine follow-up of patients who have had melanoma?
»	Does local tumor recurrence influence overall survival?
»	What is elective lymph node dissection (ELND)? When is it indicated?
»	What is sentinel lymph node biopsy? When is it indicated?
»	What is linear melanonychia?
»	What is Hutchinson’s sign?
»	What is Hutchinson’s freckle?
»	Are there any new ways to assess prognosis in patients with melanoma?
»	What forms of chemotherapy are used in the treatment of metastatic melanoma?
»	Is radiation therapy effective for melanoma?
»	How effective is immunotherapy in malignant melanoma?
»	Does gene therapy offer any better results?
»	How about local perfusion?
»	What are some newer targeted therapies for melanoma?

What are some newer targeted therapies for melanoma?

The available information regarding the molecular mechanisms underlying melanoma has increased greatly over the past several years. As noted above, the major molecular pathways that have been implicated in melanoma include p16 and p14^ARF, B-Raf, N-Ras, microphthalmia-associated transcription factor (MITF), PTEN, and Bcl2. Of particular clinical relevance is the RAS-RAF-MEK-ERK (MAP kinase) signaling pathway. Sorafenib and imatinib are oral multikinase inhibitors that inhibit MAP kinase pathway signaling. Trials of sorafenib or imatinib in combination with dacarbazine and carboplatin/paclitaxel are currently underway. Trials are also underway investigating the Bcl-2 antisense molecule, oblimersen, in combination with dacarbazine. Newer small molecular inhibitors are currently under investigation.

Tawbi H, Nimmagadda N: Targeted therapy in melanoma, Biologics 3:475–484, 2009.

Dhomen N, Marais R: BRAF signaling and targeted therapies in melanoma, Hematol Oncol Clin North Am 23:529–545, 2009.