[What's new in dermato-oncology?].
One of the major advance concerning skin carcinoma is the development of targeted therapy: anti-patch/sonic/hedgehog for basal cell carcinoma (BCC) and anti-EGFR for squamous cell carcinoma (SCC). These therapies are indicated for advanced non surgically removable tumors. Their anti-tumoral efficacy has been shown, their effect seems to be suspensive which raises the question of their tolerability for long term use. Laboratory work have shown that BCC and SCC stem cells locate in different cell compartments and follow distinct molecular events which explains their distinct behaviour. The role of HPV in EBDR skin cancers has been ruled out. Photodynamic therapy induced-immunosuppression can be prevented by lowering the light fluence. The gene responsible for the Ferguson Smith syndrome has been identified: it is the gene encoding TGFBR1. Its implication in SCC needs to be determined. A new compound, PEP005, (ingenol mebutate) should soon enlarge therapeutical options for actinic keratosis. Concerning melanoma, results of the two phase III studies using two innovative therapies (anti-Braf and ipilimumab) have been published. Comparative study between anti-Braf and DTIC has shown a response rate of 48.4 % with vemurafenib and 5.5 % with DTIC. The risk of death was diminished by 67 %. These results have allowed to switch to vemurafenib patients with progression under DTIC. However, the initial response is followed by relapse in a majority of cases. Mechanisms of this resistance have been studied and the inhibition of several molecules involved in different or identical pathway should help to resolve that problem. The combination ipilimumab+ DTIC gives better results than DTIC alone. The adverse events of this association are slightly different than those seen with ipilimumab alone. They must be known by prescribers. Some discussions are on their way between the two companies developping anti-Braf and ipilimumab to develop therapeutic strategies combining both treatments. 20 to 30 % of patients taking anti-Braf drugs will develop SCC (due to paradoxal activation of MAPK in non Braf mutated cells). PEG-interferon seems to be indicated in ulcerated melanoma with lymph node micrometastasis. Some other targeted molecules such as C-KIT and anti-MEK are under evaluation. The effect of sunscreens on melanoma risk prevention has been reported in an Australian study. A low vitamine D status is reported to have a bad prognosis in melanoma and is observed in fair skin patients at risk. Recommendations for the care and follow up of patients with Merkel carcinoma have been published. The elevated risk of positive sentinel lymph nodes in these patients does not allow to define a subgroup of Merkel patients that could be spared from the technique. Sarcoma also benefit from targeted therapy especially DFSP with imatinib. Other molecules among which mTOR inhibitors are being evaluated in sarcomas. A collaborative work has allowed to classify and evaluate in a more standardized way cutaneous T lymphomas and should help future trials. Some microRNA can be used as diagnostic tools or therapies in T cell cutaneous lymphomas. Finally a review of modern therapeutical strategies in cutaneous lymphomas has been published.
Service de dermatologie, hôpital Saint-Louis, 1 av Claude-Vellefaux, 75475 Paris cedex 10, France. nicole.basset-seguin@sls.aphp.fr
N
N
Basset-Séguin
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068818:Cetuximab; D003880:Dermatology / Q000639:trends; D020022:Genetic Predisposition to Disease; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D020249:Hormone Replacement Therapy; D006801:Humans; D007108:Immune Tolerance; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D010789:Phototherapy / Q000009:adverse effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D014807:Vitamin D / Q000097:blood
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C400134:BAP1 protein, human; D053823:Hedgehog Proteins; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D014807:Vitamin D; D019009:Proto-Oncogene Proteins c-kit; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; D043222:Ubiquitin Thiolesterase; D000068818:Cetuximab