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Clinical Oncology

FEBRUARY 20, 2019

[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

FEBRUARY 20, 2019

[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.]

Lege Artis Medicinae

DECEMBER 20, 2010

[Genomic background of asthma]

SZALAI Csaba

[From a genomic point of view asthma is a multifactorial disease. It means that the susceptibility to the disease results from interaction of several (possibly several hundred) genes; in addition, the development of the disease requires environmental factors, as well. In the last years the hypothesis-free methods became widespread in the field of genomics investigating the genomic background of diseases. These methods do not need previous knowledge about the pathomechanism of the diseases and make it possible to discover new metabolic pathways. In this review all of the new asthma genes will be presented detected in the last few years by two such methods, by positional cloning and genome wide association study. The careful design of the studies, the large populations, the robust genomic and bioinformatic methods make it likely that these genes are really asthma genes playing important roles in the pathomechanism of the disease and are potential new therapeutic targets.]

Lege Artis Medicinae

OCTOBER 20, 2005

[THE INFLUENCE OF IMMUNOGENOMIC FACTORS ON HIV-INFECTION]

FÜST György

[Authors discuss data published in the last 2-3 years indicating that besides the characteristics of the virus itself, the natural course of HIV disease is also regulated by genetic factors from the very onset till the end. Susceptibility for HIV infection of the carriers of a non-expressing mutant allele (CCR5Δ32) of one of the main coreceptors of HIV is markedly lower than that of the non-carriers. HLA-concordancy, that is few differences in the HLA alleles between the infected and noninfected partners, increases the chance of the HIVtransmittal. On the other hand, carriage of some HLA genotype e.g. that of the HLA A2/6802 supertype may significantly decrease the risk of the sexually transmitted HIV infection or that of the HIV infection from the mother to child. The rate of progression of the HIV disease which may vary in broad range from the median value of 10 years is also dependent on genetic factors. Progression is lower than the average in the carriers of the CCR5Δ32, HLA-B*27 and HLAB* 57 alleles while it is significantly more rapid in carriers of the HLA-B*35.1 allele. Recent data on the regulation by genetic factors of some sideeffects and the efficacy of combined antiretroviral treatment indicate that in the near future individual treatment may be used on the basis of the genetic background of the patients.]

Lege Artis Medicinae

OCTOBER 20, 2005

[NEW PROSPECTS IN MEDICINE BY THE APPLICATION OF BIOTECHNOLOGICAL METHODS]

KOSZTOLÁNYI György

[The recent completion of the sequence of the human genome - thanks to the developments in biotechnology - has increased interest in genetics, but confusion remains about the role of genetic information in the medical practice. The role of genomics (a term coined only 15 years ago) in medicine is even more confusing. This review summarizes briefly the most important advances relating to the robust development in biotechnology, by which the practice of medicine has entered an era where the individual patient’s genome could help to determine the optimal approach to care, whether it is preventive, diagnostic, or therapeutic.]

Lege Artis Medicinae

JANUARY 21, 2004

[A NEW DISCIPLINE IN THE CENTER OF MEDICAL RESEARCH AND CLINICAL PRACTICE - THOUGHTS ON BIOINFORMATICS]

FALUS ANDRÁS, BERKE Tamás, ORTUTAY Csaba Péter, SUHAI György

[Bioinformatics is one of the most important element of genomic research revolutionising biomedical science. This review describes the phenomena of genomic variance and comparative genomics. Briefly, the review summarises the identification procedure of new genes and gene expression patterns highly important in diagnostics. Bioinformatic procedures make possible the rapid detection of pathogens and have principal role in molecular drug design technologies.]

Lege Artis Medicinae

JULY 20, 2002

[Functional genomics - Potentials, hopes, and post genomic realism]

FALUS ANDRÁS, SZALAI Csaba, TÓTH Sára

[This paper provides an overview on major elements of the age of genomics: including the human genome programme, principles of gene chip technology and data management by bioinformatics. The manuscript provides examples from the fields of oncology, infectology and allergy. The possibility of ”in silico” research on computers is also presented with the shadows of the post-genomic era and the significance of changes in the biomedical paradigm.]