Clinical Oncology

[PI3K–AKT–mTOR pathway as a therapeutic target]


DECEMBER 10, 2018

Clinical Oncology - 2018;5(04)

[The PI3K-AKT-mTOR is one of the most busy signalling pathway, accepting and sending the message to the effector compartment. The pathway is very complex with activators (see the name), and inhibitors, as PTEN. Depending of the cell type this pathway participates in almost all functions of a given cell. The members of the pathway may have genetic failures, as a consequence, the risk for the development of different diseases, including cancer is high. Therefore it is logical to produce drugs to inhibit the dysregulated function. Unfortunately, despite the promising preclinical effectivity, so far only 4 drugs can be used to treat cancer patients. There are some hypothesis for the in effectivity, e.g. no useful marker for patient selection, high toxicity, false drivers for targeting. What is sure, combination therapy is much better than monotherapy]



Further articles in this publication

Clinical Oncology


A szerkesztők

Clinical Oncology

[Experiences – ESMO 2018]


Clinical Oncology

[Treatment of head and neck cancer]


[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Clinical Oncology

[Advancing therapies in metastatic castration-resistant prostate cancer]

GIULIA Baciarello, MARCO Gicci, KARIM Fizazi

[Introduction: Prostate cancer is the second most common cause of cancer world wide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the corner stone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatment shaved ramatically improved overall survival of men with mCRPC. Current therapies are basedon AR-axis inhibitors and taxane-based chemotherapies, aswell as radiopharmaceuticals and Sipuleucel T. Areas covered: The authors provide a review of the current fi eld of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, aswell as in non-metastatic castrationresistant patients, it is expected that a growing subgroup of patients will be expose dearlierto chemotherapy and to AR targeted agents. It becomes then fundamental to fi nd novel strategies to over come drug resistance and further improve survival.]

Clinical Oncology

[Medical use of marihuana especially in oncology]


[The medical use of marijuana has gained a considerable attention among wide range of cancer patients lately in Hungary. Consequently, oncologist sare facing questions related to cannabinoids more and more in their clinical practice. This article aims to clarify some basic concepts and to give a brief introduction on the current international and national legislation on their accessibility. Numerous publications have dealt with the application of marijuana in various indications. Among the tumour related indications, the concerned studies mainly refer to chemotherapy induced nausea and vomiting, chronic pain, sleep disorders, anorexia and cachexia. The article also to uches upon on knowledge connected to the causal treatment of malignant tumours, which are currently limited to glioblastoma. Information on the carcinogenic potential of cannabis and information on the popularity and attitudes of American oncologists can be found in this article. This paper gives a literature review in the above mentioned themes.]

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Cholinesterase inhibitors and memantine for the treatment of Alzheimer and non-Alzheimer dementias


In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients’ and caregivers’ quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer’s therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer’s dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer’s and non-Alzheimers’s dementias.

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[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

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[The history of acute stroke care in Hungary ]


[Stroke is one of the most frequent causes of death and the most important cause of permanent disability worldwide and also in Hungary. The Hungarian medical literature has mentioned this disease and has been giving recommendations for its treatment since 1690. Initially folk medicines, herbal preparations and phlebotomy were used as standard therapy. Later, cooling the head joined these methods. Pharmacy preparations emerged at the middle of the 19th century. From the middle of the 20th century, products of the pharmaceutical industry like blood flow enhancers and neuroprotective drugs were in the frontline of the acute care. Anti­hy­per­ten­sive, antithrombotic and lipid-lowering medications became part of stro­ke prevention. Imaging techniques – mainly computer tomography of the brain and ultrasound examination of the cervical large arteries – have radically changed the diagnostics of cerebrovascular diseases from the middle of the 1980s. Since the 1990s, diagnostic and therapeutic decisions are based on reliable evidence from good quality clinical trials. Since the beginning of the 21st century, reperfusion treatments (intravenous thrombolysis and mechanical thrombectomy) re­present the most effective emergency care. The current direction is the extension of the therapeutic time-window of reperfusion treatments based on sophisticated neruoimaging. This review provides a brief summary of the development of stroke care in the last three and a half centuries as reflected in the Hungarian medical literature. ]

Lege Artis Medicinae

[Hypertension, COPD and COVID-19. Focus on antihypertensive therapy]


[Chronic obstructive pulmonary disease is a very common comorbidity of hypertension and it is often unrecognised by physicians. The factors involved in the pathomechanism of both diseases should be realised when choosing treatment. Among factors, hypoxia, increased tone of sympathetic nervous system and activation of renin-angiotensin-aldosterone system should primarily be considered. Vascular wall damage and endothelial dysfunction has an important role in both conditions. The goals of treatment are elimination of risk factors, optimizing the blood pressure, the consequential prevention of cardio-cerebrovascular, renal and pulmonary damage; finally prolonging the patients’ life and improving their quality of life as well. Both hypertension and COPD significantly worsen the condition of COVID-19 patients since they increase the severity of the disease and the rate of in-patients’ and their mortality. In the treatment of hypertension among COPD and COVID-19 patients there must be emphasized the medication inhibiting of renin-angiotensin-aldosterone system, such as angiotensin-converting en­zyme inhibitors or angiotensin-II AT1 re­cep­tor antagonists. Special attention concerned the beneficial effect of mineralocorticoid receptor antagonist spironolactone. Other antihypertensive drugs (calcium channel blockers, thiazide-like diu­retics, high selectivity β1 receptor antagonists) may supplement the treatment if necessary. Long-acting β2 receptor agonists, muscarinic receptor antagonists and inhalation corticosteroids may be administered in double or triple combination also in hypertension and COPD as well. It is important to note, that statin therapy and also vitamin D3 improve the condition of COVID-19 patients.]

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Surveillance and management of patients with tuberous sclerosis complex

FOGARASI András, GYORSOK Zsuzsanna, BODÓ Tímea

Tuberous sclerosis complex (TSC) is an autosomal dominant disease due to the uncontrolled differentiation, proliferation, and migration of cells in several organs. Clinical expression is highly variable, from mild skin findings and asymptomatic brain lesions to seizures, mental retardation, autism, and potentially fatal kidney, cardiac, or pulmonary disease. Aim of this paper is to summarize the diagnostic criteria, surveillance and therapeutic issues of this multisystemic disorder emphasizing the most important neurological consequences. Presenting the state-of-the-art management recommendations and comparing them with the local protocols, we hope that our review might help in the proper assessment of one of the most important single gene disorder.