Metastatický melanom je agresivní onemocnění. Dosud využívané léčebné možnosti jako aplikace dakarbazinu, temozolomidu, high dose interleukinu-2 byly relativně omezené. Vemurafenib je malá molekula, která má schopnost inhibovat mutovanou BRAF proteinkinázu. Na základě provedených klinických studií BRIM-2 a BRIM-3, kdy vemurafenib dokázal prodloužit celkové přežití (OS) a dobu do progrese onemocnění (PFS), byl zaregistrována v EU k léčbě v monoterapii u dospělých pacientů s neresekovatelným nebo metastazujícím melanomem s pozitivní mutací V600 genu BRAF., Metastatic melanoma is an aggressive disease. Historical treatment options have been limited (e.g. dacarbazine, temozolomide, high dose interleukin-2) and associated with poor outcomes. Vemurafenib is a first-in-class, small molecule BRAFV600 inhibitor. Vemurafenib is approved in the EU as monotherapy in adult patients with BRAFV600 mutation-positive unresectable or metastatic melanoma. In the trial BRIM-2 a BRIM-3 vemurafenib significantly improved both overall survival (OS) and progression free survival (PFS) in patients with unresectable melanoma., Ivo Kocák, Ilona Kocáková, Stanislav Špelda, and Literatura
Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis. DESIGN: The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined. CONCLUSIONS: No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer., Garajová Ingrid, Svoboda M., Slabý O., Kocáková L., Fabian P., Kocák I., Vyzula R., and Lit.: 71