The function of IAP has long been limited to an inhibition of apoptosis through their capacity to bind some caspases. Since the expression of these proteins is altered in some tumor samples, IAPs are targets for anticancer therapy and many small molecules have been designed for their capacity to inhibit IAP-caspase interaction. Unexpectedly, these molecules appeared to significantly affect NF-κB activation. In this review, we will discuss the central role of cIAP1, cIAP2 and XIAP in the regulation of NF-κB activating signaling pathways.

Breast cancer is associated with a low rate of thromboembolic events (TEE) when compared to other cancers, without influence of the histological type on incidence. Risk factors include the stage of cancer, and the patients' profile and management: hospitalization, surgery and presence of a central catheter but also some cytotoxic chemotherapy, tamoxifen, and some anti-angiogenic targeted therapies. The pathophysiology of TEE includes a cross-stimulation phenomenon, involving tumor cells with procoagulant activity, and factors of hemostasis, coagulation and fibrinolysis. Circulating cellular microparticles bearing tissue factor play a major role, as well as thrombogenic platelet interactions with tumor cells via P-selectin. The occurrence of TEE in a cancer patient significantly increases the risk of death. Prevention is framed by recommendations in surgical patients. Curative treatment is based on the use of low molecular weight heparin for at least six months.

Granulocyte colony-stimulating factor (G-CSF) are frequently used in oncology and haematology practice. Respiratory disturbance has been reported during administration of G-CSF. G-CSF may induce pulmonary toxicity but this fact remains an open debate because of its frequent association with other drugs. The action of these treatments could explain a part of the pulmonary events but not completely. The specific pulmonary effect of the G-CSF is probably underestimated. Most of these pulmonary events occur in association with other risk factors, mainly when a pneumonia occurs during the neutropenia. However, G-CSF are recommended in febrile neutropenia.

Childhood cancers account for 1% of malignant tumors. As a result of advances in treatment, almost 80% of children and adolescents who currently receive a diagnosis of cancer become long-term survivors. Assessment of potential for fertility preservation should thus be a systematic element of care for children treated for a malignant tumor (high-dose chemotherapy with alkylizing agents, radiation therapy including the gonads) or those receiving hematopoietic stem cell grafts for malignant or benign disease (sickle-cell anemia, immune deficit). Potential adverse consequences of treatment include impaired puberty and fertility due to gonadal removal, genital tract injury or damage to germ cells from adjuvant therapy. Advances in assisted reproductive technologies have led to new possibilities for the prevention and treatment of infertility. Among them, cryopreservation of ovarian tissue appears to be the most promising, or perhaps the only one available before puberty with encouraging results. Nevertheless the uncertainties, or even risks, related to these treatments, should not be neglected. We review experimental data in mouse and sheep animal models. The results demonstrate that immature ovarian grafting can restore spontaneous puberty and fertility in both models. This study addresses the very important issue of epigenetics, and provides valuable information for the study of ovarian transplantation, suggesting that these procedures do not perturb normal epigenetic marks. These results are highly relevant to the question of immature cortex reimplantation.

The management of colorectal liver metastases has been improved these last years. The efficacy of chemotherapy regimens and targeted therapies has led to a better prognosis. It has also allowed the resection of metastases initially unresectable. In this setting, the pathologist plays a major role. He is involved in the gross examination, in order to perform an adequate sampling of the lesions. He is also involved at the morphological level, for the assessment of the pathological response, which is now recognized as a prognostic factor and a marker of sensitivity or resistance to a given treatment. Moreover, the determination of predictive markers of response or resistance to induction treatments will constitute a supplementary and major challenge for the pathologist.

MET is a cell membrane tyrosine kinase receptor for its ligand the hepatocyte growth factor (HGF), also called scatter factor (SF). MET conveys mitogenic, motogenic and proangiogenic signals, important during embryonic development and during the development of cancer. Activation of the HGF-MET pathway seems to be associated with a poor prognosis in lung cancer. Activation in lung cancer may be related to several molecular anomalies: ligand overexpression, receptor overexpression, genomic amplification or MET mutation. In MET amplified or mutated lung cancer, MET may be an important oncogene, as the tumor appears "MET addicted". In other lung cancers, MET may be implicated in tumour progression by tissue invasion and formation of metastases. MET amplification is also a mechanism known to be implicated in 20% of secondary resistance to EGFR inhibitors in patients presenting EGFR mutated lung cancer. Different strategies of MET inhibition in lung cancer are being studied, particularly in EGFR mutated lung cancer. In this review we discuss the structure of the MET receptor, the activated pathways, the main genomic anomalies in lung cancer and the development of MET inhibitors.

The increased incidence of cancer in dialysis patients has been discussed since the mid 1970s. Furthermore, the emergence of targeted therapies (TT) requires oncologists, nephrologists and pharmacists to question themselves about the handling of these new classes of drugs in dialysis patients. While the cytotoxic drugs have been used in oncology for a long time, these new molecules are recent and clinical studies on their management in dialysis patients are missing.

The increased incidence of cancer in dialysis patients has been discussed since the mid-70s. Consequently, oncologists, nephrologists and pharmacists are increasingly facing challenging situations of cytotoxic drug handling in dialysis patients. In dialysis patients, two main issues must be considered. First, renal function of hemodialysis (HD) patients is no longer functional. Therefore, these patients may necessitate drug dosage reduction, namely drug prescription, must be cautiously checked before administration with appropriate dosage adjustment whenever necessary to ensure efficacy while avoiding overdosage and related side effects. Secondly, drug clearance by dialysis must be taken into account for appropriate chemotherapy timing in order to avoid drug removal, which may result in a loss of efficacy.

Anticancer drug management is complicated especially in renal insufficiency patients, a frequent situation in oncology. Several aspects need to be taken into account: first, the dosage. In this population, the kidney fails to eliminate drugs. Consequently, dosage adjustment can be necessary for drugs with pharmacokinetic profile altered by renal insufficiency in order to avoid dose-related side effects due to accumulation of the drug. Secondly, renal tolerance is an important aspect of anticancer drug management as renal insufficiency is a risk factor for developing renal side effects. Prevention of renal side effects is essential and means to limit this toxicity should be used, especially with hydration. Finally, it is essential to consider all the treatments prescribed in renal insufficiency patients in order to avoid accumulation of nephrotoxic drugs.

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study, which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients, treated in 15 cancer centers. Among them, 7.2% had a SCR level ≥ 110 mmol/L. In the 1,898 patients with breast cancer, only 31 patients (1.63%) had a SCR level ≥ 110 mmol/L. Nevertheless, respectively 51.8 and 50.8% had a creatinine clearance estimated with the Cockcroft-Gault and aMDRD formulae, below 90 mL/min. Even if the most used medications (anthracyclins, taxanes, trastuzumab, hormone therapies) are not nephrotoxic, these results are important because bevacizumab modifies the need for renal management. In case of renal insufficiency, some other treatments such biphosphonates IV, capecitabin and platin salts need drug dosage adjustment or interruption.

Myopic choroidal neovascularization (CNV) is the first cause of CNV in young patients. The aim of this study was to compare the efficacy of intravitreal injections (IVT) of ranibizumab with photodynamic therapy (PDT) in this indication.

Refractory thyroid cancers include medullary and differentiated cancers with locally advanced disease that is not amenable to surgery or with distant metastases, differentiated thyroid carcinomas being refractory to radio-iodine treatment and all anaplastic carcinomas. These carcinomas are rare, with an estimated incidence in France of 350 new cases per year. Their management may benefit from the TUTHYREF network. Kinase inhibitors inhibit kinases of the VEGF receptors, and this inhibits angiogenesis, and some of these agents also inhibit other kinases of the MAPkinase pathway. These inhibitors are effective in differentiated and medullary thyroid cancers, and induce a partial response or a long-term stabilisation in more than half of patients. Their toxicity is significant and these treatments should be given only to selected patients with locally advanced or metastatic disease, with progression or with clinical symptoms.

Antimetabolites are cytotoxic agents, which have been developed for more than 50  years. Which cancer patient did not receive or will not receive 5-fluorouracil or methotrexate during the evolution his or her disease? Antimetabolites are defined as interfering with the synthesis of the DNA constituents; they are structural analogues, either of purine and pyrimidine bases (or the corresponding nucleosides), or of folate cofactors, which are involved at several steps of purine and pyrimidine biosynthesis. Their first mechanism of action is, therefore, to induce depletion in nucleotides inducing in turn an inhibition of DNA replication. However, some of them are able to get inserted fraudulently into nucleic acids, inducing structural abnormalities leading to cell death by other mechanisms, including DNA breaks. We present in this paper, for the three classes of antimetabolites, both ancient and recent molecules as well as molecules still in clinical trials, without exhaustivity.

Nuclear topoisomerase I (Top1) is involved in the relaxation of DNA supercoiling and plays a pivotal role in the coordination of essential DNA processes such as transcription, replication, DNA recombination and DNA damage signalling. For all these reasons, Top1 has been an attractive target for the development of anticancer drugs, which poison Top1 by trapping the enzyme on its DNA cleavage sites, which results in irreversible DNA lesions that are responsible for their cytotoxicity. They derive from the natural compound camptothecin and two derivatives are approved in the clinic, topotecan and irinotecan; other compounds such as indolocarbazoles and indenoisoquinolines are in development. However, the efficacy of these drugs is often limited by the problem of resistance, which involves various mechanisms at different steps of drug action, from drug transport and/or metabolism to the signalling and/or repair of the DNA lesions that are generated. A better understanding of these mechanisms is a major concern for the future development of new Top1 inhibitors and the identification of biomarkers that could be used to predict tumour response to these drugs in the clinic and to adapt the treatment to each patient.

Adrenocortical cancer (ACC) is a rare aggressive malignancy with a poor prognosis (5-year survival: 45 %). Their management requires multidisciplinary expertise. Complete resection by an expert surgeon is the only curative treatment. Very few adjuvant treatments are available and their efficacy is not fully proved. Adjuvant mitotane therapy increases the disease-free survival in the majority of patients after surgery but further studies are needed to determine patients in whom this treatment is the more beneficial. Blood concentrations of mitotane between 14 and 20mg/l are necessary to have a full efficiency but this therapeutic window may cause side effects difficult to control. When aggressive parameters are present, radiotherapy is proposed. In case of residual or unresectable disease, combination of chemotherapy and mitotane is conventionally proposed. FIRM-ACT study establishes that EDP (etoposide, doxorubicine et cisplatine) is the most effective chemotherapy for progressive ACC. The first results of treatment with tyrosine kinase inhibitors, in patients with progressive disease despite one or two lines of chemotherapy are disappointing but this may be partly explained by the interaction with mitotane which reduces the plasma concentrations of sunitinib in particular. Clinical trials are underway to assess the effectiveness of other targeted therapies, including treatments acting on the IGF-1 receptor.