Clinical Oncology

[EMT (Epithelial-Mesenchymal transition) – CSC (Cancer Stem Cells)]

KOPPER László

FEBRUARY 10, 2018

Clinical Oncology - 2018;5(01)

[The effi cacy of the antitumor therapy is usually limited due to the resistance against the chemotherapy. One of the most important reason of the secunder resistance is the intratumoral heterogeneity, which is the consequence of the variety tumor phenotypes in the same tumor. Such clonal heterogeneity develops during the tumor growth or tumor therapy. The cancer stem cells (CSC), according to the concept, can determine the progression of the tumor, including metastatization, which probably the major enemy for clinical oncology. This activity of CSC, in tumors with epithelial origin, is supported by a change from epithelial to mesenchymal phenotype (epithelial-mesenchymal transition); but not entirely. The CSC phenotype is very similar to characteristic of the normal stem cells, as resistance, self-renewal etc. The mechanisms of these concepts is known only partially, but the technical advances contribute to the identifi cation of key genetic and epigenetic regulatory pathways. If such improvement becomes real, we can be much ahead both with markers and therapeutic targets.]

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[Last time we have described about the modern treatment of hepatocellular carcinoma (HCC) in „Klinikai Onkológia” in 2014 (1) and a detailed guideline regarding epidemiology, treatment according to BCLC staging system has been published as well in a special edition in this year (2). Here, we discuss mainly the fi rst- and second line systemic treatment of HCC according to our experience and the new results of clinical trials. 203 patients were treated in our Department between 2010 and 2016. These results have been presented already on the MKOT conference in 2016. In this year we have started second line systemic therapy with regorafenib in 9 cases.]

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[Over the last several decades, local control (LC) for rectal cancer has markedly improved because of advances in surgical technique and the adoption of adjuvant or neoadjuvant chemoradiotherapy (CRT). Total mesorectal excision (TME) during surgical resection of localized rectal cancer, which involves removal of the entire circumferential perirectal tissue envelope, decreases rates of both involved surgical margins and local recurrences. Similarly, for patients with locally advanced rectal cancer (LARC), including T3 and T4 tumors and lymph node-positive disease, adjuvant and more preferably neoadjuvant CRT has exhibited the ability to both improve disease-free survival (DFS) and LC. Some patients undergoing neoadjuvant CRT achieve a complete pathologic response (pCR) to CRT and the oncologic outcomes are particularly favourable in this group. In contrast to improved local control, patients’ overall survival rates are in need of improvement, and the major factor limiting the outcome is the appearance of metachronous distant metastases. The main approach to overcome this issue is the escalation of systemic therapy in the neoadjuvant setting, e.g. by addition of induction or consolidation chemotherapy before or after neoadjuvant chemoradiotherapy (the so-called total neoadjuvant treatment, TNT, approach). The aim was to present a short overview of the role of radiotherapy and radiochemotherapy in the management of rectal cancer with a focus on current treatment stand wasards for locally advanced rectal cancer.]

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[The role of early clinical studies in oncology]

KERPEL-FRONIUS Sándor

[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

Clinical Oncology

[Foreword]

A szerkesztők

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