Clinical Oncology

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]

KOPPER László, NAGY Noémi, SEBESTYÉN Anna

MAY 10, 2017

Clinical Oncology - 2017;4(02)

[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

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Clinical Oncology

[Foreword]

A szerkesztők

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[Geriatric oncology has an increasing role since in several types of cancer the median age at diagnosis is above 60 years of age. The treatment of elderly patients are frequently set back by prejudice, stereotypes and lack of information. All these lead to the fact that even in well-developed countries elderly cancer patients often do not receive the necessary treatments. This is even more true in poor-countries, where the fi nancial defi cit accumulated in health care is often attempted to be reduced by the treatment of elderly. If a paediatric oncology patient does not get suffi cient cancer treatment there is a fi erce protest, but everybody is silent if this occurs in the case of an 80 years old patient. For this unacceptable situation both authorities (fi nancing) and professional bodies (treatment, education) are responsible. Clinical data show that elderly cancer patients get the same benefi t of active oncology treatment, as younger ones. Age on its own does not contraindicate any cancer treatment. The aim of this review is to prove by data, that elderly cancer patients should also get active oncology treatment. The questions of assessment include frailty, the relationship of cancer development and ageing, and other problems related to the oncology treatment of elderly patients are also discussed.]

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[Increasing experimental and clinical evidences demonstrated the synergic effect between the rapidly implemented immunotherapy and advanced forms of focal radiotherapy, not only on the elimination of the irradiated lesion, but also on the enhancement the immune-mediated systemic anti-tumoral activity. It is essential for gaining the most benefi t from the combination of the two modalities to select the appropriate patients, to defi ne the irradiation parameters, such as radiation quality (ie. particle) dosage, (total dose, fraction number) size of the target volume, the use of other supportive and anti-tumor drugs. In this review, we provide an update for the daily oncological practice on the data accumulated up to now on the molecular basis and patomechanism of enhancing radio-immune effect and clinical results, and highlight the most important parameters, which may increase the abscopal effect of ionizing radiation, thereby increasing the effectiveness of immunotherapy. However, development of clinical guidelines for benefi cial integration of immunotherapy and radiotherapy could be expected after evaluation the result of currently ongoing numerous (> 100) clinical trials. If the preclinical results will be confi rmed clinically, it could lead to paradigm shift in the use of ionizing radiation.]

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