memo - Magazine of European Medical Oncology

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0185-8

Hilbe, W.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0180-0

Aberger, Fritz; Eberl, M.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0176-9

The past years of intense research on the role of major developmental signalling pathways and their implication in human diseases, have identified the Hedgehog, Wnt and Notch pathways as aetiologic factors in a wide variety of human malignancies. The Hedgehog signalling cascade, originally identified in the fruit fly Drosophila melanogaster, orchestrates a considerable number of developmental processes during vertebrate embryogenesis, including cell proliferation, survival, pattern formation, differentiation and stem cell fate. In the adult organism, however, the pathway is mostly inactive or only transiently activated during regeneration and healing, where Hedgehog signalling apparently controls stem cell activation and self-renewal. By contrast, many human malignancies such as cancers of the brain, skin, gastrointestinal tract or prostate display elevated and persistent activation of the Hedgehog pathway either in the bulk of tumour cells, the adjacent stromal compartment or in tumour-initiating cancer stem cells. Recent results from studies using different preclinical cancer models unambiguously show that uncontrolled Hedgehog pathway activation can induce or contribute to cancer development and growth and that targeted pathway inhibition is likely to offer an efficient therapeutic opportunity. We review here the oncogenic role of Hedgehog signalling, particularly the different mechanisms by which aberrant Hedgehog signalling affects malignant growth. We then focus on recent data from clinical trials that provide proof-of-concept for a striking therapeutic benefit for patients treated with small molecule Hedgehog pathway inhibitors.

Gunsilius, E.; Drach, Johannes

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0175-x

The treatment of multiple myeloma (MM) has undergone significant developments due to the incorporation of novel agents (thalidomide, bortezomib and lenalidomide), which has improved the clinical outcome of patients with MM. This review summarizes the most recent results and represents a treatment recommendation for MM patients in the routine clinical setting.

Pfeilstöcker, Michael

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0179-6

Iron overload has been identified as important factor influencing the clinical course of patients with myelodysplastic syndromes. Chelating agents are available for the treatment of iron overload. Given the lack of data from prospective studies on the effects of iron chelation on the outcome of MDS patients, several guidelines for the use of chelators have been published. This article compares these guidelines and reviews the evidence for the recommendations.

Krieger, Otto

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0177-8

Allogeneic stem cell transplantation (SCT) is the only curative treatment in Philadelphia positive chronic myeloid leukaemia. Because of the good results of Imatinib and the toxicity of transplantation SCT has lost its place in first line treatment of CML. In the last decade a new modality of SCT (with reduced intensity conditioning = RIC-SCT) was used to lower treatment mortality (TRM) of SCT and to transplant also elderly patients (over 50 years), even with comorbidities. A.Gratwohl published a risk score for SCT (EBMT score) to categorize patients with low, intermediate and high TRM. An useful tool is also the comorbidity index (HCT-CI) of Sorror to define patients for different transplant procedures (standard SCT vs. RIC-SCT). Stem cell transplantation is indicated in CML patients, who have no adequate response to Imatinib or second tyrosine kinase inhibitors (TKI), in patients after accelerated phases or blastic crisis and in patients (with low EBMT score) with mutations, which predict a failure to TKI therapy. For these patients a projected 5-year survival range between 50 and 70%.

Sun, W.; Walder, A.; Fiegl, Michael

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0174-y

In the last decade, many novel immunomodulating therapies and “biologicals”, usually acting as signal transduction inhibitors, came into routine therapy in cancer. Mostly, these substances are well tolerated, and there is a typical spectrum of common side effects to be considered with these therapies. A rather rarely seen toxic effect associated with the administration of these agents is haemolytic anaemia (HA). Here, we shortly summarize current knowledge on HA potentially triggered by these substances. Furthermore, an impressive case of myelodysplastic syndrome with 5q deletion which received lenalidomide and developed autoimmune haemolytic anaemia (AIHA) is presented.

Grusch, M.; Berger, Walter

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0182-y

The fibroblast growth factors (FGFs) are a large family of peptide growth factors playing essential roles in embryonic development, tissue maintenance and wound healing. FGFs interact with target cells by binding to four high-affinity receptor tyrosine kinases (RTK) termed FGFR1-4. Based on the proliferative and anti-apoptotic as well as pro-angiogenic functions of the FGF/FGFR signal module, it is not surprising that deregulations occur at multiple levels in many types of human cancer. Recently, it got obvious that FGF/FGFR signals might also be hyperactivated in non-small cell lung cancer (NSCLC) by diverse molecular mechanisms leading to autocrine support of tumour cell proliferation, migration and survival as well as paracrine activities including neo-angiogenesis. Additionally, FGF/FGFR signals turned out to be involved in therapy resistance against not only classical chemotherapy but also novel targeted anti-NSCLC agents like inhibitors of the epidermal growth factor receptor (EGFR). This suggests that FGF/FGFR inhibitors might represent a novel component for combined NSCLC therapy approaches.

Pircher, Andreas; Heidegger, I.; Gunsilius, E.; Hilbe, W.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0181-z

Tumour angiogenesis has been identified to play a critical role in tumour growth and tumour progression. Multiple angiogenic factors are involved in the regulation of angiogenesis. Amongst them VEGF (vascular endothelial growth factor) and its receptors (VEGFRs) are of crucial relevance. Inhibition of VEGF/R signalling by monoclonal antibodies or small molecules as receptor tyrosinekinase inhibitors has already been successfully established for the treatment of various cancer entities. Bevacizumab, a monoclonal antibody against VEGF, as well as sorafenib and sunitinib, both small molecules, are already approved for clinical practice. Furthermore, an ever-expanding list of new anti-angiogenic agents is under advanced clinical development, some of which are already being considered for approval. However, not all patients treated with anti-angiogenic therapies benefit from this kind of therapy and in most cases, the effect is transient. Therefore, there is an urgent need for biomarkers to identify patients likely to benefit from anti-angiogenic treatments, to select the optimal dose and to understand the mechanisms of resistance. Preclinical models suggest multiple mechanisms involved in acquired or primary resistance against anti-angiogenic therapies, but only few data are available from clinical studies evaluating surrogate markers during therapy. The present review summarizes the different types of biomarkers for anti-angiogenic therapies and gives an overview of resistance mechanisms to anti-angiogenic therapies.

Fridrik, Michael

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0178-7

This review discusses the complexities of different endpoints in clinical trials. A definition of these endpoints and their value for specific situations will be evaluated.

Gautschi, O.; Pless, Miklos

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0171-1

The Swiss Group for Clinical Cancer Research (SAKK) is a non-profit organization that conducts multicentre clinical trials for patients with many different types of cancer, including thoracic malignancies. This article summarizes the history and structure of the SAKK, and discusses the rationale and the present status of active SAKK trials in patients with non-small cell lung cancer, small cell lung cancer and malignant mesothelioma.

Zielinski, Christoph; Brodowicz, Thomas; Just, Dagmar

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0184-9