Clinical Oncology

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


FEBRUARY 15, 2016

Clinical Oncology - 2016;3(01)

[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.]



Further articles in this publication

Clinical Oncology

[News from the World]

Clinical Oncology

[Treatment of mesothelioma - an update]

MOLDVAY Judit, HEGEDŰS Balázs, KOVÁCS Ildikó, DÖME Balázs

[Malignant pleural mesothelioma is an aggressive tumor arising from the mesothelial cells lining the pleura. It is an asbestos related disease with increasing incidence both in Europe and in Hungary. This often fatal disease is characterized by rapid progression, and unfortunately, treatment options are very limited to date. Thus every effort should be made to better understand the pathological and molecular biological characteristics of this disease in order to develop new treatment strategies. This summary reviews the treatment options available today as well as the new therapeutic approaches at the experimental and clinical investigation stage.]

Clinical Oncology

[Epigenetics and cancer]


[Epigenetics is concerned with the modulation of the genom without structural changes in the nucleotide-sequence. The main target in the regulation of epigenetical activity is gene expression. The main mechanisms in epigenetics the reversible chemical modulation of the DNA and the histones which are regulated by enzyme-complexes, acting directly with the metabolism and the signaling pathways, as well as with the sensors of macro- and microenvironment. New members of the epigenetical family are the non-coding RNAs (e.g. microRNA). The misregulation of these components can infl uence the tumors at different stages of growth and progression. Several inhibitory anticancer drugs (e.g. azacytidine, decitabin, vorinostat, romidepsin, belinostat) are used in the clinical targeted therapy.]

Clinical Oncology

[Surgical view on the perioperative oncological treatment of liver metastases originated from colorectal cancer]


[Recent development of surgery resulted in fundamental changes in assessment of resectability of liver tumors. Surgical interventions became more radical and more effective. Colorectal liver metastasis (CLM) represents the most frequent hepatic tumor, where therapeutic options require close collaboration between surgeons and oncologists, and up-to-date approach from both. As the fact is, that CLM is a metastasis of a primary colorectal carcinoma, it seems to be obvious to apply perioperative chemotherapy. Results justify serious precaution. Neoadjuvant chemotherapy did not improve overall survival. Several data testify, that even perioperative chemotherapy is not indicated in these cases. Adjuvant chemotherapy can be applied after extended liver resections and two stages hepatectomies. About 20% of patients with initially inoperable CLM may be rendered resecable after systemic chemotherapy. Prognosis of synchron CLM is bad, 5 year survival is less than 20%. Disappearing CLM needs special respect, high level of perfection in liver surgery is essential. After chemotherapy postoperative morbidity is rising, technical diffi culties may occur. Further studies are required to examine possible effect of new targeted molecular therapy-based regimens on resectability. Individualized multidisciplinary treatment planning is mandatory.]

Clinical Oncology


A szerkesztők

All articles in the issue

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


[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.]

Clinical Oncology

[Oncological management of gastro-entero-pancreatic neuroendocrine neoplasias]


[Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are unusual and relatively rare neoplasms. They characteristically synthetize, store and secrete a variety of peptides and neuroamines, which can lead to development of disctinct clinical syndromes. Clinical symptoms and presentations vary depending on the location and hormones produced by the tumor. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. An update of the WHO classifi cation has resulted in a new classifi cation dividing neuroendocrine neoplasms into neuroendocrine tumors (NETs) including G1 (Ki67 index ≤2%) and G2 (Ki67 index 3-20%) tumors and neuroendocrine carcinomas (NECs) with Ki67 index >20%, G3. The different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are discussed in this overview.]

Clinical Oncology

[EGFR family and gynecologic cancers]


[The HER family of receptor tyrosine kinases may potentially play an important role in gynecologic malignancies. Amplifi cation and overexpression of various HER family members including epidermal growth factor receptor (EGFR/HER1) and HER2 have been reported in epithelial ovarian cancer and endometrial carcinoma as well as in cancer of the uterine cervix. High expression of EGFR has been associated with poor prognosis independent from histiotype while HER2 expression may be more histotype dependent. This review summarizes the clinical experience with anti EGFR/HER2 directed monoclonal antibody therapy in the three major gynecologic cancer types to date.]

Clinical Oncology

[Molecular profi les in therapeutic strategy]

PETÁK István, SCHWAB Richárd

[In 2013, 10 years after the completion of the human genome, the cancer genome project has identifi ed almost all possible cancer genes, which could be responsible for the malignant transformation and progression. These genes are called „driver” genes, and the pathogenic mutations to be „driver” mutations. The census of „driver genes” in 2013 counted 138 genes and 1.5 million mutations. The situation is further complicated by the fact that up to 8 „driver” gene can be activated simultaneously in the same tumor, furthermore, the profi le may change during tumor growth and metastatization. 2013 was a turning point also because several targeted therapies were registered. Currently there are about 30 targeted drugs in clinical use and more than 200 targeted compounds in clinical development. This means that in 3-4 years the number of drugs will at least double. Most of the current patients can only access these compounds in clinical trials. But, patient already benefi t signifi cantly more even from phase I clinical trials, if they are selected based on the molecular profi le of the tumor. Fortunately, the advancements of next generation sequencing technologies provide the opportunity to identify all „driver” genes, - the whole molecular profi le, - in the patient’s tumor for the cost of one month targeted therapy. But the information generated can be only used in clinical practice if the results are processed by „molecular info-bionics”.]

Lege Artis Medicinae

[Treatment of EGFR mutant lung adenocarcinoma after progression]

BOGOS Krisztina

[Precision medicine proposes the personalization of health services in order to make the best individual decisions about the interventions and treatments for the patient. Molecular genetic diagnostic tests help to select the appropriate therapy, so-called targeted therapy. In the case of extensive lung cancer with EGFR mutation, EGFR tyrosine kinase inhibitors are immediately applicable; they are very effective and can reach long-term remission of the disease. However, resistance mutation can develop during the treatment, which causes the progression of the disease; therefore change of therapy is needed. In our case, we show the possibility of targeted treatment beyond the progression, emphasizing the importance of detecting resistance mutation. ]