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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Further articles in this publication

Clinical Oncology

[Foreword]

A szerkesztők

Clinical Oncology

[News from the World]

KLINIKAI Onkológia

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[New results from San Antonio Breast Cancer Symposium, 2017]

KAHÁN Zsuzsanna

[SABCS 2017 has been a 40-year jubilee conference with festive appearance and content. The anniversary provides possibility to look back: today we fi nd the knowledge and practice as of twenty years ago schematic and rough while the changes are overwhelming. Therapy became colorful and personally. There is need for precisious care which means consideration all patient and tumor features when surgical or medical therapy, radiotherapy or even diagnostic issues are decided - this has been the most important message of the conference this year. The Symposium always provides the most modern and breakthrough approaches and attitude that support advancement in patient care.]

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[Treatment of hepatocellular carcinoma - an update]

DEMETER Gyula, VÉGH Éva

[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.]

Clinical Oncology

[Solid organ transplantation and malignancies]

VÉGSŐ Gyula, MÁTHÉ Zoltán

[Recent breakthroughs in the fi eld of organ transplantation and oncology have challenged existing views, and necessitate the revision of several tumor-related issues in transplantation. The need for expanding the donor pool raises the question of how and when it is plausible to transplant the organs of a donor with a history of cancer, such that the risk of tumor inoculation and manifestation due to the graft would be minimal for the recipient. Another point to consider is whether it is acceptable to transplant a recipient with a history of a malignant tumor, and if yes, how much tumor-free survival time is required as a minimum before the transplant. Transplanted patients live longer as a result of modern immunosuppressive therapy. However, the risk of malignant tumors increases proportionally to the length of the immunosuppressed state: their incidence may be as much as 20-30% in the long term. The signifi cance of „de novo” posttransplant tumors is highlighted by the fact that they are among the leading causes of death in transplant patients. Taken together, malignant diseases pose a serious problem from several aspects, the solution for which requires close teamwork of experts in oncology and transplantation, and the integration of up-to-date knowledge in the process of making a therapeutic decision, tailored individually for the patient.]

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Hypertension and nephrology

[Infections associated to vesicoureteral reflux disease in children below 1 year of age: the infulence of continuous antibiotic prophylactic therapy on the prevalence of resistant pathogenic bacteria]

MÁTTYUS István, KENESEI Éva, VÁSÁRHELYI Barna

[Background: The primary goal when children with vesicoureteral reflux disease (VUR) are treated is the prevention of pyelonephritis and persisting renal damage. Continuous antibiotic prophylaxis (CAP) is usually applied to reach this aim. The selection of resisting pathogens is the major risk of CAP. The aim of our survey was to describe the patterns of pathogenic strains leading to pyelonephritis in patients treated with and without CAP. Patients and method: The pathogenic strains implicated in pyelonephritis were identified in 48 and 56 children below 1 year of age who were treated with or without CAP, respectively, between years 2006 and 2011. Results: Breakthrough urinary tract infections developing in the presence of CAP are more frequently (with about a double risk) caused by polyresistant bacteria compared to infections that emerged without CAP. Nevertheless, it should be noted that the prevalence of resistant pathogens was about 40% even in infants without CAP. Discussion: The pattern of pathogenic strains leading to pyelonephritis alters significantly even in the cohort of children below 1 year of age treated with CAP to prevent infections associated to VUR. The risk may be decreased through the rational use of antibiotics. To reach this goal national guidelines on VUR should be updated and the role of additional non-antibiotic treatment should be established.]

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KOPPER László

[Genetic fusions are the cosequence of genomic rearrangement including chromosomal inversion, interstitial deletion, duplication, amplifi cation, translocation. Fusions can influence tumor development and progression. Fusions fi rst discovered in hematological malignances (e.g. BCR-ABL), butlater more and more were identified dueto the higly sensitive NGS. It has been found that the oncogenic fusions are in minority in a given tumor. Today, some fusions were apprevedas targets (ALK, ROS1, PDGFB) by FDA. Asino ther targeted therapy resistance is in evitable, which is a very important challenge for newly designed drugs.]

Lege Artis Medicinae

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Lege Artis Medicinae

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KOPPER László

[In most cases, the targeted therapy is able to produce clinical response, but after a certain interval it turns to be ineffective due to secondary resistance against the therapy. One of the most demanding challenge in treatment of cancer is to prevent or inhibit such resistance, which could have several forms, e.g. appearance of new driver activating mutations in the treated tumor, clon(s) existed in minority with different mutations (targets) can grow and replace the temporarely sensitive tumor cells (on the basis of tumor heterogeneity); another pathway takes over the role in cancer progression, etc. Such problems are very common in the RAS-RAF-MEK-ERK pathway. These are very important proteins to collect extracellular signals in order to regular different cell functions, especially proliferation. With activating mutations make the RAS-pathway independent from the normal .regulation. To inhibit the consequence of the mutations is largely still an unsolved problem, with few exceptions (e.g. inhibition of BRAF mutations). Theoretically, the inhibition of the next steps of the pathway, MEK and ERK, may stop the pathologically activated signals, partly due to their inhibition, and party to effi ciently decrease the feedback inside the pathway. This review discusses aspects of this possibilities, especially to overcome resistance and prolong the effectiveness of therapy.]