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Non‑small cell lung cancer with EGFR mutations

05/2018 Prof. MUDr. Jana Skřičková, CSc., Mgr. Blanka Robešová, Ph.D., MUDr. Ondřej Venclíček, MUDr. Bohdan Kadlec, Ph.D., MUDr. Marcela Tomíšková, MUDr. Lenka Jakubíková, Ph.D., MUDr. Jana Špeldová, MUDr. Zdeněk Merta, CSc.
In the case of non-small cell lung cancer (NSCLC), the existence of somatic mutations in the epidermal growth factor receptor (EGFR) gene and their effect on the sensitivity to the treatment of tyrosine kinase inhibitors (TKI) is known. Mutations occur in the tyrosine kinase domain between EGFR exon 18 and 21, predominantly point deletions and deletions, eventually insertions. In exons 19 and 21, 80-90% of known activating mutations of EGFR are concentrated. The so-called activation mutations include the G719X point mutation in exon 18, the L858R and L861Q point mutations in exon 21 and the deletion in exon 19. Among so-called resistant mutations are the insertions in exon 20, the T790M and S768I point mutations in exon 20, and the D761Y mutation in exon 19. The mutation rate of the EGFR gene in the Caucasian population is 10%. In NSCLC patients experiencing activation mutations for EGFR, the most effective treatment is with tyrosine kinase inhibitors. In our paper, we investigate the activation and resistance mutations of the EGFR gene and provide an overview of the results of first, second and third generation of TKI treatment.
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Neuroendocrine neoplasm

05/2018 MUDr. Marcela Tomíšková, MUDr. Lenka Jakubíková, Ph.D., MUDr. Bohdan Kadlec, Ph.D., MUDr. Jana Špeldová, prof. MUDr. Jana Skřičková, CSc.
Neuroendocrine pulmonary neoplasms are a group of rare tumors. Their incidence is 1.35 cases per 100,000 inhabitants. They form a heterogeneous group from well and moderately differentiated carcinoids to very aggressive low differentiated carcinomas. Diagnosis is based on pathomorphology, immunohistochemical examination and neuroendocrine differentiation. Individual types of neuroendocrine pulmonary neoplasms (differ from one another by localization, biological behavior, clinical picture, diagnosis, and treatment approaches. Low differentiated carcinomas (LCNEC, SCLC) are aggressive, sensitive to chemotherapy and radiation but have a poor prognosis. For well and moderately differentiated neuroendocrine pulmonary neoplasms (typical and atypical carcinoid) captured in operable stage, surgical removal of the tumor leads to its complete cure. Analogs of somatostatin receptors, peptide receptor radionuclide therapy or m-TOR inhibitor (mammalian target of rapamycin) represent a new therapeutic potential in treatment of recurrent or inoperable neuroendocrine pulmonary neoplasms grade I and II.
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Short nivolumab causing severe fatigue with long‑lasting partial response – a case reports

05/2017 MUDr. Lenka Jakubíková, Ph.D., MUDr. Jana Špeldová, MUDr. Marcela Tomíšková, prof. MUDr. Jana Skřičková, CSc.
The authors of the first part of the article summarize the current therapeutic results of nivolumab in both squamous and non-squamous lung cancer, as well as the safety profile of this type of immunotherapy, including recommendations for prevention and measures for the occurrence of side effects. In particular, adverse events, particularly weakness and exhaustion, were reported in two selected patients who experienced a severe fatigue with the need for permanent discontinuation of treatment immediately after initiation of treatment with nivolumab, but two months after the last dose of immunotherapy, partial healing response that lasted for one year in both patients was observed.
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