Clinical Oncology

[Liquid biopsy in clinical oncology – fine-tuning precision medicine]

PRISKIN Katalin, PINTÉR Lajos, JAKSA Gábor, PÓLYA Sára, KAHÁN Zsuzsa, SÜKÖSD Farkas, HARACSKA Lajos

FEBRUARY 20, 2019

Clinical Oncology - 2019;6(01)

[The classical method of genetically characterising a tumour requires tissue biopsy with which a small sample is removed from the affected organ. This sample represents the tumour in the further analyses. However, the localised nature of sample collection limits representative characterisation. The so-called circulating tumour DNA, isolated from blood plasma after a simple sample collection, potentially enables the oncological analysis of all tumour tissues carrying genetic alterations that can be identifi ed as markers. In order to maximally exploit the potentials of circulating tumour DNA, we must adjust the analytical tools to its specifi c features. The preanalytical handling and storage of the sample signifi cantly infl uences its further usability. In order to be able to detect a potential mutation in a mostly wild-type background, the development of new, specifi c methods is needed, most of which are based on next-generation sequencing techniques. In the past decades, the pronounced decrease in the costs of such techniques led to an accumulation of an immense amount of genetic information on tumorigenesis. Due to the development of sequencing technologies, the turnaround times of tests also decreased enabling their employment in routine care besides research. Starting from our research, this can be realised via three approaches: technological development, the implementation of our already existing diagnostic methods in liquid biopsy, and the construction of well-planned disease-specifi c gene panels. Based on international trends and our experience in serum diagnostics, we are certain that liquid biopsy will become a central pillar of oncological screening and precision oncology in the near future.]



Further articles in this publication

Clinical Oncology

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]


[Breast cancer is globally the most frequent malignant disease in women with increasing incidence. Meta-analyses using data from a large set of patients combining genetic and standard clinicopathological features provide valuable models in predicting disease risk, outcome and therapy response. With the advent of molecular technologies, the amount of available data generated for each tumor and each patient is growing exponentially. The increased data availability allows the development of new innovative systems enabling to discover more effective prognostic and predictive biomarkers. The goal of this review is to summarize meta-analyses that utilize data from countless patients to provide breast cancer risk prediction (Gail-model, Claus-model, BRCApro, IBIS, BOADICEA), and prediction of prognosis and expected therapy response (PREDICT, Magee). In the last part of the review we introduce online analytical tools (KMplot, ROCplot) developed to examine, rank and validate new prognostic and predictive biomarker candidates.]

Clinical Oncology

[P53 – the suppressor]


[Our basic nature requere cells quantity and quality to perform differenciate activity. p53 has the responsibility for quick out those cells who carries molecular failures in DNA avoiding transfer mutations into doughter cells. If the DNA-repair insuffi cient p53s with on apoptosis. Whe p53 is mutated the phenotypes are different in a wide range due to the heterogenity of the DNA damages, and also the expression pattern of a suppressor protein. With the increasing amout the damaged DNA the genomic instability elevates D the risk to development of tumors. It is linict mutated gene could be a promosing tr, 10t for therapy. So far the attempts have little value for the clinic.]

Clinical Oncology

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Oncology

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

[The role of artifi cial intelligence in precision medicine]

MESKÓ Bertalan

[The essence of practicing medicine has been obtaining as much data about the patient’s health or disease as possible and making decisions based on that. Physicians have had to rely on their experience, judgement, and problem-solving skills while using rudimentary tools and limited resources. With the cultural transformation called digital health, disruptive technologies have started to make advanced methods available not only to medical professionals but also to their patients. These technologies such as genomics, biotechnology, wearable sensors, or artifi cial intelligence (AI) are gradually leading to three major directions. They have been (1) making patients the point-of-care; (2) created a vast amount of data that require advanced analytics; and (3) made the foundation of precision medicine. Instead of developing treatments for populations and making the same medical decisions based on a few similar physical characteristics among patients, medicine has shifted toward prevention, personalization, and precision. In this shift and cultural transformation, AI is the key technology that can bring this opportunity to everyday practice.]

All articles in the issue

Related contents

Clinical Oncology

[Oncogene-targeted therapy of non-small cell lung cancer]


[Lung cancer is the leading cause of cancer related deaths thus presenting one of the main public health related issues globally. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, platinum-based chemotherapy was the mainstay of systemic therapy for NSCLC, leading to median survival rates of only 8 to 10 months. Major improvement in the treatment of NSCLC was made through the identifi cation of key genetic aberrations (oncogene drivers) that drive tumor initiation, maintenance and progression and development of highly effective oncogene- directed therapies. Oncogene-directed therapies against epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in conjunction with well-validated methods for the detection of their targets already represent a standard care of advanced NSCLC patients. Encouragingly, in the recent years a number of additional genetic aberrations have emerged as novel molecular targets with potential therapeutic implications in lung cancer. In this review a comprehensive overview of standard oncogene-directed therapies of advanced NSCLC is provided, challenges in overcoming resistance to those therapies are discussed and novel oncogene-directed therapies under development are briefl y presented.]

Clinical Oncology

[Treatment of hepatocellular carcinoma - today]


[The hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death globally, and at the same time, it is the main event leading to death in cirrhotic patients. In the etiology of HCC, the non-alcoholic liver disease may be an important cause besides the viral cirrhosis. The HCC’s staging systems (Child-Pugh scores, Cancer of the Liver Italian Programme/CLIP, Barcelona Clinic Liver Cancer/ BCLC) play an important role in predicting the prognosis and determining the appropriate therapy. In Europe, the treatment strategy is based on the BCLC staging system. Screening of cirrhotic patient is also important because curative therapy is available only for the early-stage HCC. Several therapeutic options exist in the intermediate stage disease; among them the radiofrequency ablation (RFA), the transarterial chemoembolization (TACE) and the percutan ethanol injection (PEI) are most important. For the advanced disease, the only approved systemic therapy is sorafenib, which has been well-tolerated and yielded a substantially relative improvement in overall survival. For patient in end-stage disease with impaired liver function or a poor performance status, only supportive care is recommended.]

Lege Artis Medicinae

[Opportunities in drug therapy of biliary tract cancer. Past - present- future]


[Biliary tract cancer is relatively rare tumour, but the dismal prognosis renders it frightful. Biliary tract cancers which consist of gall bladder cancers and bile duct cancers can be cured only with surgery thus it is exceedingly important that the surgery should take place in dedicated centres. The multidisciplinary approach may involve drug therapy, too, as an adjunct to surgery or for palliation. This publication summarizes present data about systemic treatment with some chronological point of view. Starting from therapeutic nihilism of the past and projecting anticipatory development of the future it shows the present state of medical treatment in this patient population.]

Clinical Oncology

[Prevention and therapy of cervical cancer ]

RÉVÉSZ János, BÍRÓ Mátyás

[The global incidence of cervical cancer is ~530000, the death rate is ~270000 per year. These data shows, that cervical cancer is the fourth common malignancy in woman worldwide and the leading cancer related death in developing countries. HPV infection is the most important factor of carcinogenesis. Immunisation against HPV can prevent infection, and decrease the cancer incidence. In case of invasive cancer the therapeutic principles are surgery and radiotherapy. In case of high risk patients and/or locally advanced disease the adjuvant and neoadjuvant cytostatic treatment has limited evidences. The traditional cytotoxic therapy and the recent antiangiogenic therapy recommended for patients who have extrapelvic metastasis, residual tumor after primary radiotherapy or recidiv non curable tumor by radiotherapy or radical surgery.]

Clinical Oncology

[Non-surgical treatment of the biliary tract and gallbladder cancer]

PIKÓ Béla, LACZÓ Ibolya

[Biliary tract cancers are rare, hence only a few high level of evidences related to their treatment are available. The successful treatment and the only chance for long-term survival are based on the radical surgical resection. After the fl uoropyrimidin based protocols chemotherapy regimens prefer gemcitabine combinations (cisplatin, oxaliplatin, capecitabine) or FOLFIRINOX, considering the patient performance status as well. There are no registered targeted therapy in this indication, the most experiences were acquired with erlotinib; nowadays the optimal treatment can be selected by the molecular genetic profi le of the tumour and not by the results of the clinical studies. The radiotherapy and the radiochemotherapy can be administered preoperatively, postoperatively and for palliation as well, in addition to the conventional percutaneous radiotherapy, brachytherapy, intensity-modulated radiotherapy, intraoperative irradiation, radioembolization can also be administered depending on the technical equipments. Besides the photodynamic therapy and several ablation therapies, even interventional radiological procedures can play a signifi cant role.]