Clinical Oncology

[Angiogenesis – antiangiogenesis]


SEPTEMBER 05, 2015

Clinical Oncology - 2015;2(03)

[Tumor growth requires vascularization to be supplied by oxygen and nutritients. The vascular network could be different between tumors, even during the development of the same tumor (local and systemic spreading), from the occupation of already present vessels to the real angiogenesis (i.e, proliferation of endothelial cells). Moreover, the tumor cells can create channels, mimicking the normal vessels. This spectrum in morphology should be refl ected in the therapeutic response, in the effectiveness of antiangiogens, but the how is unknown. It is sure that acceptable clinical activity can be achieved only with combinations, both with traditional cytotoxic and targeting drugs. The clinical advantage can be hampered by increased toxicity, demanding supportive actions. One of the key decisions is to select the proper therapy considering the patient and the tumor characteristics (today increasingly at molecular level) and predict the response to the therapy. Such (bio)markers are still missing, although intensive research trying the best. Since the main target of antiangiogenic drugs (today and tomorrow) the VEGF/R family, a useful marker is expected from them. The inhibition of angiogenesis is a logical step against the solid tumors and these steps slowly but steadily can improve the patients life-time, as well as their quality of life.]



Further articles in this publication

Clinical Oncology

[A structured approach to test the clinical benefi t of treatments of advanced cancer]


Clinical Oncology

[Ablation of liver cancer]

DOROS Attila

[Ablative therapies of the malignant liver tumors are used frequently all over the world. It is a very well tolareted minimally invasive treatment, followed by a short observation period. Patients might be sent home within 24 hours. Nowadays, there is suffi cient data supporting its effectiveness in the treatment of early primary liver cancer, equalling the results of surgical resection. The situation is different in liver metastasis, especially from coloectal cancer. In these cases ablative techniques have a supporting role, limiting their action on the multimorbid patients and small non-resectable tumors. These facts and trends - worldwide and in Hungary - are discussed, focusing on effectiveness, places in therapeutic protocols and domestic diffi culties.]

Clinical Oncology

[Up-to-date treatment of head and neck cancers]


[The head and neck squamous cell cancer is often detected at an advanced stage, resulting in dismal prognosis despite the relevant developments of the oncotherapy in the last decades. The introduction of new techniques, new drugs and combinations though improves the survival for certain subgroups of patients, meanwhile the organ-function preservation and side effects reduction approaches lead to improved quality of life. The preventive-supportive care prior and during the therapy (dental care, nutrition, toxicity management) and the complex rehabilitation has paramount importance. MRI and 18FDG PET-CT and the advanced methods of molecular pathology became part of the diagnostic work up. The selection of the therapy based on the tumor characteristics, HPV detection, on the patient’s condition and wishes, as well as on multi-disciplinary team decision based on the available technical options. Early stage tumors can be successfully treated either by surgery alone or by radiation therapy. For locally advanced cases concomittant chemo-radiotherapy stays in the axis of the complex management using advanced radiation technique (IGRT-adaptive- IMRT) with cisplatin (or if contraindicated with cetuximab), which could be complemented by induction chemotherapy and/or surgery. Several new approaches are currently being tested in clinical studies after establishment of cisplatine-cetuximab treatment for recurrent/metastatic tumors. In the future, detection of molecular processes and driver mutations could result in development of more effective targeted anti-tumor agents, and individual molecular tumor profi le guided therapy, including the various forms and combinations with emerging immunotherapy.]

Clinical Oncology

[Treatment of testicular germ cell tumors – an up-date]

BAKI Márta

[The frequency of germ cell tumors is about 1% of all male cancers. The incidence increases in developed countries. The prevalence is the highest among the young males. The histologic type, extent of disease and therapy is based on international guidelines. The surgery, radio- and chemotherapy can achieve cure in the germ cell cancer patients. Regarding the late toxicity, the minimal invasive tumors are suggested to keep on the wait and see policy. The complex therapy of poor risk groups reached more than 80% permanent remission rate. The chemotherapy is based on cisplatin, but in second and third line therapy paclitaxel, gemcitabin and oxaliplatin is widely used. After the cure of germ cell cancer patients the careful follow up is mandatory.]

Clinical Oncology

[Mucositis - prevention and therapy]

NAGY Zsuzsanna, VALTINYI Dorottya

[Side-effects are critical challenges in cancer therapy. These complications can threaten the quality of life, sometimes the life itself. One of the most frequent side effects is mucositis, the damage of mucosa, either in the oral cavity (oral mucositis, OM), or in the gastrointestinal tract (gastrointestinal mucositis, GIM). Prevention is a key action for the effi cient supportation. Recognition of OM is relative easy, but of GIM is rather diffi cult. The risk factors could come from the patients and/or can be caused by the therapy. The successful management of mucositis mostly depends on the cooperation of the patient, which is highly infl uenced by the success of care (e.g. decreasing the level of pain). In general, mucositis (especially oral mucositis) a well managable disease, burt more informations are required to increase the quality of prevention and therapy. Such expectation could be realized by specifi c and sensitive biomarkers, however, they are still missing]

All articles in the issue

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[Ways of imaging the expression of vascular endothelial growth factor and its receptor]


[The vascular endothelial growth factor (VEGF) and its receptors (VEGFR) signal-transduction pathway play a key role in the regulation of angiogenesis. It was originally isolated as a selective mitogen for endothelial cells and as a powerful vascular permeability increasing factor. The vascular imaging techniques make the quantification and localization of blood vessels possible. They have been used to assess blood flow, oxygenation, and vascular permeability. Also, they can be used to examine the molecular and cellular difference in the vascular wall. To evaluate tumour vascularity, a multimodality approach is expanding. VEGF as the primary mediator for vascular-permeability is indirectly measurable with DCE-MRI (dynamic contrastenhanced MRI). MRI investigation can determine the ratio of deoxyhemoglobin/oxyhemoglobin in order to localize the hypoxic regions in vivo (BOLD [blood oxygen-level dependent] sequence and OMRI [Overhauser MRI]). In molecular MRI (mMRI), contrast agent-mediated alteration of tissue relaxation times can allow for the detection and localization of molecular disease markers. To localize the expression of VEGFR with SPECT and PET, antibodies and VEGF isoforms can be marked with isotopes. VEGFR is an excellent candidate for targeted ultrasound imaging since it is almost exclusively expressed on activated endothelial cells. Optical imaging is a relatively cheap method suitable so far primarily for small animal studies.]

Hungarian Immunology

[The role of endothelium, cell migration, chemokines and angiogenesis in inflammatory rheumatic diseases]


[Endothelial cells, leukocyte-endothelial interactions and angiogenesis are highly involved in the pathogenesis of inflammation and thus in that of inflammatory rheumatic diseases. As this research area is very progressive, one needs to review novel molecular mechanisms and new therapeutic approaches in this respect. Authors review the most important functions of endothelial cells, the process of leukocyte extravasation, tissue infiltration and their cellular and molecular basis. Endothelial cells themselves produce a number of inflammatory mediators including interleukin-1 (IL-1), IL-6, IL-8, chemokines and others. Among cell adhesion molecules, β1 and β3 integrins, as well as E-, L- and P-selectins and their respective ligands have been implicated in leukocyte-endothelial adhesion. In recent years, numerous inflammatory mediators, cytokines, chemokines and proteases have been implicated in angiogenesis and angiostasis. Hypoxia, the vascular endothelial growth factor (VEGF)-angiopoietin system and mechanisms driven by β3 integrins are of major importance during angiogenesis. Significant amount of data have become available of the regulation of cell adhesion, migration and neovascularisation. Adhesion, chemokine and angiogenesis research has important clinical, practical aspects for antirheumatic and anti-cancer therapy. VEGF antagonists, anti-integrin antibodies, chemokine and chemokine receptor inhibitors, as well as thalidomide are currently in the first line of development.]

Clinical Oncology

[Challenges in Molecular Targeted Therapy for Gastric Cancer: Considerations for Effi cacy and Safety]

KEI Muro

[The Cancer Genome Atlas Research Network recently proposed a molecular classifi cation for gastric cancer (GC) into four subtypes based on comprehensive evaluation. While the mechanisms of molecular targeted therapies in GC were confi rmed by multiple clinical studies, only a limited number of therapeutics for GC have been approved to date. In this systematic review of the available literature, we discuss the completed and ongoing clinical trials of molecular targeted therapies in patients with GC, with a focus on their effi cacy and safety. Results of recent studies clearly demonstrated that trastuzumab and ramucirumab, monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), respectively, improved overall survival (OS) in GC with manageable safety profi les. Careful surveillance of ongoing clinical trials and timely profi ling and monitoring of genetic signatures are imperative to establish a strong foundation for precision medicine in GC.]