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Immunotherapy of lung cancer

05/2019 MUDr. Bohdan Kadlec, Ph.D.
Immunotherapy, a new modality in the treatment of non-small cell lung cancer, provides patients with advanced disease with the possibility of effective treatment with less toxicity. Immune checkpoints treatment utilizes highly selective humanized monoclonal antibodies in order to reactivate anti-tumor response. This treatment improves overall survival, extends the spectrum of treatment options, and is less toxic compared to chemotherapy. Immune-mediated adverse reactions can lead to a variety of clinical conditions and can include any organ in the body. While the indication of immunotherapy is likely to expand in the future, further knowledge is needed to determine the optimal combination with chemotherapy, radiotherapy and other anticancer drugs, as well as finding optimal biomarkers to predict the therapeutic effect and toxicity of immunotherapy.
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Atezolizumab for the treatment of advanced non‑small cell lung cancer

05/2018 MUDr. Bohdan Kadlec, Ph.D.
Atezolizumab (Tecentriq®) is a new drug from a number of immunotherapeutics and the first programmed death-ligand (PD-L1) antibody approved for metastatic non-small cell lung cancer patients who have progressed during frontline chemotherapy. Atezolizumab is an antibody to PD-L1 engineered to avoid antibody-dependent cell-mediated cytotoxicity of activated T cells that may express PD-L1 and activates the tumor-specific immune response while preserve immune homeostasis in normal tissue by sparing the interaction of PD-L2 with PD-1. The approval was based on two open-label phase II/IM multicenter trials, that demonstrates good safety profile and benefit for atezolizumab in overall survival, progression-free survival, and response rate when compared to docetaxel regardless of PD-L1 expression. A prospective role in the first line in combination with chemotherapy and bevacizumab appears to be a promising one.
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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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