Skin cancer may manifest in a simple solar keratoisis (sunburn scar) which is easily removed with cryosurgery in a GP's surgery. A black freckle should be examined for a possibly benign pre-cancerous lesion. Simple precautions could offset the onset of melanoma. Maps of cancer concentrations regularly show people in coastal areas have a higher incidence of melanoma, possibly due to an outdoor sun-exposed lifestyle.
Current Treatments
Melanoma (skin cancer) treatments such as interferon (IFN), dacarbazine (DTIC) and high dose interleukin-2 (IL-2) had no confirmed effect on overall survival rates from melanoma. IL-2 standard therapy in the US had significant toxicity, requiring expensive inpatient treatments.
Promising Therapeutic Approaches
The benefit from immunotherapy may be limited by the ability of T cells to infiltrate a tumour. Obviously the greater the degree of immune infiltration the better the outcome. Some 24% of tumours have a high degree of immune infiltration.and are more likely to respond to high dose IL-2 to record a median progression free survival of 19.4 months (JCO 27: 15s, Abstracts 9003).
Novel Immunotherapy
Ipilimumab is a novel type of immunotherapy which allows T cells to continue to expand. Two antibody blockers, ipilimumab and tremilimumab, produce responses in 8–15% of patients with refractory (troublesome) melanoma, extending survival in 20–30% of patients to more than two years.
PD-1 Antibodies and Inhibitors
Tumour expression of PD-1 ligand may prevent immune response from functioning normally even with a blockade inducing T cell death. Controlling immune regulation may aid the immunotherapy of patients with melanoma.
PD-1 antibodies and PD-1 inhibitors may provide more tumour specific immune suppression. When binding to tumour or antigens expressing PD-ligand1, this causes aptosis or exhaustion of the immune cells. Blocking this interaction may restore the activity of the immune system selectively within tumours (Journal of Clinical Oncology Abstract/28/15/2506). More than 50% of patients had tumour shrinkage at different dose levels in this study.
Targeting Melanoma at the Molecular Level
More than half of melanomas have K mutations in the B-RAF specific area as manifested in moles or in non chronic sun damaged skin. A study of PLX4720 inhibited tumour growth in B-RAF mutant tumours resulted in tumour response in 70% of patients, including one complete response (New England Journal of Medicine 353:809-819).
Developments in 2011
Novel immunotherapies, specific tumour therapies, anti-angiogenic therapies and selection for molecular profiling provide hope for melanoma patients in future.
Sources
- Cancerworld
- This writer has written permission from Cancer World magazine to write a series of articles on cancers with poor prognosis.
Michael Manning - ' The best lack all conviction while the worst are full of passionate intensity' W.B.Yeats
