Clinical Oncology

[Defi ciency of DNA-repair]

KOPPER László

DECEMBER 10, 2016

Clinical Oncology - 2016;3(04)

[The cell uses the DNA to keep those information, which are vital to function properly. It is essential to maintain the integrity of the DNA, the stability of the genome. Since DNA damages, caused by external or internal factors, are continuously produced, DNA-repair mechanisms should be ready to identify and eliminate the damages. Either the repair system is successful and the cell can continue its duty, or, if the damages are unrepaired, the programed cell death (apoptosis) is activated according to the rule, that it is prohibited to transfer genomic/epigenomic damages into the daughter cells. It is true that the severness of the damages are not the same. The most important is the identifi cation and repair of those damages which can make genomic instability increasing the risk of cancer development. This may happen when the repair system is insuffi cient, sometimes due to inherited mutations (e.g. BRCA1 mutations can increase the risk of breast cancer, ovarian cancer etc.). Among the damages the DNA double strand breaks are rather common, and also, that the breaks are intended to be repaired in most cases. However, if such repair fails, the cell, here the cancer cell, due to the overhelming damages will dye. This phenomenon is the synthetic lethality. An example: „cooperation” of inherited BRCA1 mutation and PARP-inhibition, can lead to clinical response using PARP inhibitors, as oliparib. New agents and clinical trials intend to take advantage from synthetic lethality.]

COMMENTS

0 comments

Further articles in this publication

Clinical Oncology

[Foreword]

A szerkesztők

Clinical Oncology

[News from the World]

Clinical Oncology

[Chemotherapy of multiple myeloma]

MIKALA Gábor, CEGLÉDI Andrea, CSACSOVSZKI Ottó, SZEMLAKY Zsuzsanna, PETŐ Mónika

[Multiple myeloma is a multifaceted haematological disease, a plasma cell malignancy that may pose an oncological differential diagnostic challenge. The importance of this disease is emphasized by its incidence. Since there are multiple novel therapies available for myeloma patients, decade-long survival in not uncommon; therefore, myeloma patients provide a signifi cant part of the patients referred to hematological clinics. In this review, fi rst the novel diagnostic criteria are introduced, followed by the standard therapeutic approaches for transplant-eligible and ineligible patients. As the disease nearly always relapses, the later line therapies available in this malignancy are presented with a special emphasis on the Hungarian haematological practice.]

Clinical Oncology

[Individualized treatment of advanced/metastatic adult soft tissue sarcomas]

SZŰCS Zoltan, JONES L. Robin

[Considering the extreme histological heterogeneity of soft tissue sarcomas (STS), their management is an art of its own. Over the last decade the treatment of STSs has been slowly shifting towards a more individualized, histology driven tailored approach. With the availability of novel antineoplastic agents and the differential sensitivity of different subtypes of sarcomas to these drugs, we aim to provide some guidance in terms of optimal sequencing of therapies. Furthermore, we discuss some of the emerging targeted therapies currently evaluated for the palliative treatment of the more common and some of the very rare STS subtypes.]

Clinical Oncology

[Biopharmaceuticals]

LÉVAY György

[Biopharmaceuticals represent a new class of very effective medications in the management of debilitating and often life-threatening diseases but the costs of these therapies exceed the costs of regular therapies. Biological medicinal products (i.e. smaller proteins or monoclonal antibodies) are mostly complex macromolecules, produced by microbial or mammalian cell cultures in bioreactors through application of complex process technologies. After patent expiry, the production of compounds with comparable quality features and comparable clinical safety and effi cacy profi les become available, however, the complexity of the macromolecules means they are not equivalent in the sense of small molecule generics. Biologics that are similar to a given licensed reference compound and meet regulatory requirements within this context can be termed as biosimilars. The similarity of the two products must be appropriately proven during the products’ marketing-authorisation procedure. As more and more biosimilar compounds have been approved by regulatory authorities in the EU and US it is expected that these products will bring signifi cant healthcare savings and much greater patient access to these revolutionary therapeutics.]

All articles in the issue

Related contents

Clinical Neuroscience

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy

UNAL Yasemin, KARA Murat, GENC Fatma, OZTURK Aslan Dilek, GÖMCELI Bicer Yasemin, KAYNAR Taner, TOSUN Kursad, KUTLU Gülnihal

Purpose - Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that “DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder”. DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. Materials and methods - Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. Results - We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. Conclusion - The methylation of NKCC1 can be a mecha­nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

Lege Artis Medicinae

[IDENTIFYING HELICOBACTER PYLORI WITH DNA-BASED ASSAYS]

RUZSOVICS Ágnes, MOLNÁR Béla, TULASSAY Zsolt

[The DNA-based assays have the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori DNA. Markers used include general H. pylori structures and pathogenetic factors like ureaseA, cagA, vacA, iceA. DNA or bacterial RNA for polymerase chain reaction (PCR) assays can be collected from gastric biopsy, gastric juice, stool, buccal specimens. PCR can yield quantitative and genotyping results with sensitivity and specificity that approaches 100%. A clear trend in the direction of the determination of quantitative H. pylori infection by real-time PCR can be observed. Fluorescent in situ hybridisation (FISH) and restriction fragment length polymorphism (RFLP) are suggested for routine antibiotic resistance determination. To identify the DNA structure of organism and its virulence factors may be feasible by using oligonucleotide microarray specifically recognising and discriminating bacterial DNA and various virulence factors. DNA based H. pylori diagnosis yields higher sensitivity, however, specificity requires sophisticated labour environment and associated with higher costs.]

Lege Artis Medicinae

[MYELODYSPLASTIC SYNDROMES - NEW THERAPEUTIC OPTIONS]

GADÓ Klára

[Myelodysplastic syndrome is a heterogeneous group of acquired clonal disorders of the haematopoietic stem cell characterized by ineffective haematopoiesis, peripheral cytopenia, and a high risk of progression to acute leukaemia. It is a common malignant disease with an increased incidence in the elderly population. Classification is based on a 1999 WHO recommendation, in which morphological features as well as clinical and cytogenetic characteristics are taken into account. Combined with the International Prognostic Scoring System (1997), it is suitable to predict prognosis and response to therapy. Clinical features include symptoms caused by anaemia, infections, and bleeding. Diagnosis is based on peripheral cytopenia and dysplastic morphology, as well as normal or increased cellularity in the bone marrow, with more than 10% of dysplastic cells. The verification of cytogenetic abnormalities is important both for confirming the diagnosis and predicting the prognosis. When designing the treatment strategy, it is essential to take the risk of leukaemia into account. On the other hand, the general state of the patient and the presence of accompanying diseases should also be considered. The goal of the treatment is to increase cell count and to decrease transfusion requirement, eventually to improve quality of life. Supportive therapy is an essential part of the management. In addition, growth factors, immunosuppressive and immunomodulatory agents, low-dose chemotherapy may be applied. Today, cure can only be achieved by allogenic stem cell transplantation. Recent findings in the epigenetic intracellular regulation allowed the definition of new therapeutic targets to develop drugs such as inhibitors of DNA methyltransferase and histone deacetylase.]

Clinical Oncology

[Adjuvant treatment of breast cancer]

PAJKOS Gábor

[Choice of optimal adjuvant treatment has been based on present debates, doubts and commit offence against processing or existing evidences. Clinical research has been resulted changes and renewal of practice decisions continuously. 3rd Breast Cancer Consensus Conference held on Kecskemét last year corresponded by Hungarian experts of the fi eld has given up to date and well-defi ned guideline. Present paper try to give a summary of adjuvant treatment courses for early breast cancer in consideration of last results of research since then.]

Clinical Oncology

[Complex medical treatment of non small cell lung cancer - new challenges, new possibilities]

OSTOROS Gyula, SZONDY Klára

[Previously, it was suffi cient to differentiate small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) in the decision making process for the therapeutic strategy of lung cancer. Recently, the situation has changed signifi cantly. There are only few new cytotoxic agents, and platinum based chemotherapy remains the standard combination in the treatment of NSCLC. In the last decade no further development has been discovered in the treatment of SCLC. However, the new molecular diagnostic and therapeutic possibilities have altered dramatically the management of NSCLC. NSCLC could not be considered as a separate entity anymore. The complex medical treatment of advanced NSCLC includes the molecular target driven therapies the histopathological subtype based chemotherapies and the immunotherapy. Immunotherapy is a new challenge in the treatment of lung cancer. Tumor-vaccines, inhibition of immune checkpoint pathways are investigated in clinical trials. Ongoing studies will defi ne the true effi cacy of these drugs. The complex combination of genes, proteins, different molecular pathways and patients characteristics, called “panomics”, are all parts of the treatment of lung cancer in the daily clinical practice.]