Magyar onkologia
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Review
[Unblocking antitumor immune response: novel possibilities for the immunotherapy of melanoma].
Recent advances in tumor immunology, a better understanding of mechanisms regulating the immune response has led to experimental and clinical testing of a novel type of immunotherapeutics: antibodies blocking negative regulatory mechanisms of T-cell activation [corrected]. The application of the CTLA-4 antagonist ipilimumab, the prototype of this new class of immune stimulating agents, represents the first treatment that resulted in significant prolongation of the survival of metastatic melanoma patients in randomized, controlled trial, leading to the approval of its use for the therapy of these patients in 2011. Together with the BRAF inhibitor vemurafenib, which was also approved in 2011, ipilimumab has changed the standard therapy of metastatic melanoma, and also paved the way for other agents aiming at influencing immune regulating molecules, of which antibodies blocking the PD-1 pathway also showed promising clinical activity. ⋯ The spectrum of side effects is different from that of conventional therapies, and a large part of them is caused by the enhanced systemic immune activity. In order to spare non-responding patients of the severe side effects and to increase response rate, the search for biomarkers that could help in identifying patients likely to react to the treatment represents an important focus of studies. Furthermore, development of combinations with other immunotherapeutic modalities, chemo- or targeted therapies may further increase the efficiency of immunomodulatory antibodies.
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[Characterization of genetic alterations in primary human melanomas carrying BRAF or NRAS mutation].
Human malignant melanoma is one of the most aggressive forms of skin cancer with an exceptionally bad prognosis. Melanoma often displays constitutively activated MAPK pathway through BRAF or NRAS mutations. It is also known that these mutations are almost never simultaneously present and that they appear at early stages and preserved throughout tumor progression, although it is proved that these alterations alone are insufficient to cause tumor progression. ⋯ Using a data mining algorithm we also found a gene alteration signature in the MAPK pathway that was commonly related to the presence of BRAF mutation in our melanoma cohorts. The second aim of this study was to develop an accurate Q-PCR method for determining the co-amplification pattern of six candidate genes that reside in the 11q13 amplicon core. We found that co-amplification of these candidate genes or the CCND1 amplification along with either BRAF or NRAS mutations might be more important for prognosis than the presence of these alterations alone.