Clinical Oncology

[The role of EGFR receptor family in the oncological practice]


DECEMBER 10, 2015

Clinical Oncology - 2015;2(04)

[The EGFR receptor family is a set of membrane tirosine kinase receptors with signifi cant homology which are responsible for cellular activation through intracellular signaling due to ligand binding. The four members of the family (EGFR1, EGFR2/HER2/neu, EGFR3/HER3, EGFR4/HER4) earned special interest in tumor biology while becoming one of the most potent targets of anti-cancer therapies. Changes in the receptor expression or in the kinase activity fundamentally modify cellular functions, survival and tumorigenic potential. Moreover, mutations are associated with reduced or altered treatment effi cacy. The basic function and major genetic and biological mechanisms affecting the function of EGFR receptors and related therapies are subjects of this overview.]



Further articles in this publication

Clinical Oncology

[Non surgical treatment of urinary bladder cancer]

PIKÓ Béla, LACZÓ Ibolya

[According to our present knowledge the surgical intervention in the treatment of bladder cancer is essential, but some non-surgical treatment methods play an indispensable role as well. Super- fi cial (non-muscle-invasive) form of bladder cancer can be treated by intravesical chemotherapy or BCG instillation, radiotherapy; the muscle-invasive forms of this tumour (≥pT2a) need neoadjuvant, adjuvant chemotherapy, radiotherapy or radio-chemotherapy. In case of metastatic disease (or locally advanced, recurrent disease) the treatment regimen consist of chemotherapy (given as fi rst line or second line), palliative radiotherapy, interventional methods, radio-isotope therapy and symptoms relief drugs. We present each of the therapeutic modalities and their indications category based on the ESMO and NCCN guidelines.]

Clinical Oncology

[The role of physical activity in oncology]


[Although nowadays there are a lot spoken about the role of physical activity in illness prevention, however it is barely connected to the treatment of malignant diseases. The regular exercises can improve physical performance and fi tness; increase muscle mass; change the body composition and proportion favorably. The positive psychological effects can decrease distress and depression; improve mood of patient; increase self-confi dence and self-respect. Finally, all of these will result in an improved quality of life. The malignant disease and the treatments can draw down either short-term or long-term consequences and side-effects that can largely infl uence or restrict everyday life. Most of them could be essentially reduced by the help of a physiotherapist experienced in oncology adopting a well-defi ned and customized workout.]

Clinical Oncology

[Current treatment of gastrointestinal lymphomas]


[The most common extranodal site involved by lymphoma is the gastrointestinal tract. The majority of extranodal lymphoma cases are of the non-Hodgkin subtype. Usually, the involvement of the gastrointestinal tract by nodal lymphomas is secondary, the primary gastrointestinal localisation is rather rare. The most common pathological types are diffuse large B-cell lymphomas and extranodal marginal zone lymphomas of the mucosa-associated tissue (MALT) subtype. Although the primary gastrointestinal lymphoma can involve any part of the gastrointestinal tract, the stomach is the most frequently involved site. The treatment and prognosis are determinated primarily by the histologic type of lymphoma, the stage of disease and the patient’s age and general condition. Helicobacter pylori (HP) infection is one of the major risk factors for gastric lymphomas, the presence or abscence of which radically infl uences the effectivity of treatment. In case of HP positivity, HP eradication itself can result in complete remission. In most cases the treatment is immuno- and/or combination chemotherapy, which is performed according to the internationally accepted protocols, specifi c to the type of lymphoma. Radiotherapy plays a lesser role in the treatment of GI lymphomas, while surgery is performed almost only in complicated cases, such as haemorrhage, occlusion or perforation.]

Clinical Oncology

[Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra]


[Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to patient with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of survival. The GETUG-AFU-15 and CHAARTED studies assessed the effi cacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in patients with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (~75%) and patients with metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUGAFU- 15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT versus ADT alone. The GETUG-AFU-15 did not fi nd a signifi cant difference in the primary end point of overall survival (OS) [hazard ratio (HR) 0.9 (95% confi dence interval (CI) 0.7-1.2); P = 0.44] for ADT plus docetaxel versus ADT alone. The CHAARTED study met the primary end point of OS [HR 0.61 (95% CI 0.47-0.80); P = 0.0003], and in a subset analysis reported the greatest improvement in OS for patients with high-volume disease [HR 0.60 (95% CI 0.45-0.81); P = 0.0006]. The following review debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study.]

Clinical Oncology

[Hematopoietic stem cell transplantation for solid tumors in adults]

GOPCSA László Zsolt, MASSZI Tamás

[We revised the medical literature regarding autologous and allogeneic hematopoietic stem cell transplantation (HSCT) in the setting of solid tumors. Autologous-HSCT for solid tumors in adult patients show changing patterns in past decades with decreases numbers for many types of solid tumors. Most marked is the previously well-described increase and decrease in autologous HSCT for breast cancer (BC). Autologous-HSCT for BC has been an area of intense controversy. The role of autologous-HSCT for BC at high risk of recurrence (at least four involved axillary lymph nodes) has been assessed by several randomized trials. Overall, it was shown that high-dose therapy prolonged disease-free survival when used as adjuvant therapy, and showed a benefi t on overall survival in only selected cohorts of patients. In second or further relapsed or primary refractory germ cell tumor, highdose therapy is considered to be a standard therapeutic option, especially when poor prognostic factors are present. In addition, sequential therapy with two to three cycles is felt to be superior to single cycle of HSCT. High-dose therapy can be regarded as a potential clinical option in selected adult patients with Ewing’s sarcoma and medulloblastoma. Currently, in other types of solid tumors the autologous- HSCT is generally not recommended or developmental and only used in the context of prospective studies. Numbers of allogeneic HSCT for solid tumors remained stable low number throughout the recent years. Transient increase is observed over the last decade and is primarily due to renal cell carcinoma, BC and colon cancer. Concepts of allogeneic HSCT for solid tumors do not rely on highdose chemotherapy and tumor load reduction but rather on a graft-versus-tumor effect. Attempts to improve the therapeutic effect of allo-HSCT or other cellular therapies in solid tumors by innovative clinical strategies are underway.]

All articles in the issue

Related contents

Clinical Oncology

[Management of pancreatic cancer today]


[Pancreatic cancer (PC) is a major health problem with a poor prognosis. The number of patients with PC is increasing globally. There are no screening tests for early detection of PC, but even when diagnosed early, surgery is possible in only a minority of cases. Managing PC remains a big challenge. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging. In patients with resectable disease, adjuvant chemotherapy improves the fi ve year survival rate, whereas the use of adjuvant radiochemotherapy is still controversial. In metastatic cancer, monotherapy with gemcitabine remained the main therapeutic option during more than 10 years. Many different combinations with other drugs and new targeted therapies have been tested with gemcitabine. Only a combination of erlotinib and gemcitabine has shown a modest survival benefi t until now. Many gene alterations that directly contribute to pancreas tumorigenesis have been identifi ed or are under active investigation. Recently, the FOLFIRINOX regimen has been reported to be more active than gemcitabine in selected metastatic patients. Quality of life is an extremly important factor, when treating a patient with PC. CA 19-9 serum level can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. There is a strong need for other predictive biomarkers to select patients, who might benefi t from available and new therapeutic options.]

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.]

Clinical Oncology

[Metals and cancer]

VETLÉNYI Enikő, RÁCZ Gergely

[We often tend to forget about our environment when looking for the origin of a disease. Inhaled air, drinking water and food, substances in contact with the skin all have an effect on the human body. Metals are indispensable parts of our everyday lives, their mining, processing and use cause a continuous exposure to them. Metal exert their effects on the body in various ways. Many of them are essential for maintaining homeostasis, but excessive or harmful metal intake can lead to health damage, including tumour formation through multiple attack points. Metals substitute each other during different transport processes and in the structure of proteins, they cause oxidative stress and bind to DNA, thereby damaging it. Applying them appropriately, the proapoptotic effect of the metal compounds is brought to the fore, thus becoming a therapeutic tool for tumours. Nowadays, platinum(II) compounds are widely used as chemotherapeutic agents and there are many ongoing studies to fi nd metal compounds with an ideal therapeutic and side-effect profi le. The aims of this article were to draw the attention to the dangers of metals in relation to cancer and to highlight their diverse application possibilities in current and future cancer therapy and diagnostics.]

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

[Inhibition of proteasome in cancer therapy]


[The ubiquitin-proteasome pathway is the most important element in the regulation of intracellular protein metabolism. Its main function is the degradation of the unnecessary proteins either as part of normal metabolic balance or in case of misfolding or part of the deregulation as in cancer cells using proteolytic enzymes. The importance of this pathway has been acknowledge by Nobel prize. In certain diseases as in several malignancies, where the ubiquitin-proteasome pathway is not able to remove the proteins due to dysfunction or accumulation in a high quantity. The unregulated accumulation of proteins could lead to cell death. This phenomenon was proven by the appearance of proteasome-inhibitors targeting mainly myeloma. It should be mentioned that clinical aspects myeloma has been discussed in an excellent review by Mikala and his colleagues in Klinikai Onkológia.]