Ibrutinib (Imbruvica®) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton's tyrosine kinase (BTK). Ibrutinib has been approved in USA in February 2014 and in France in October 2014 for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation. In clinical studies, ibrutinib induced an impressive overall response rate (68%) in patients with relapsed/refractory MCL (phase II study). In CLL, ibrutinib has shown to significantly improve progression-free survival, response rate and overall survival in patients with relapsed/refractory CLL, including in those with del 17p. Ibrutinib had an acceptable tolerability profile. Less than 10% of patients discontinued their treatment because of adverse events. Results are pending in other B-cell lymphomas subtypes such as in diffuse large B-cell lymphoma and in follicular lymphoma. An approval extension has already been enregistered for Waldenström disease in USA in January 2015. Given its efficacy and tolerability, ibrutinib is an emerging treatment option for patients with B-cell malignancies.

Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients.

Since the early 1970's, investigators at Station Biologique de Roscoff (SBR), France, have been using marine organisms as models to describe molecular pathways conserved through evolution in mammalian cells (e.g. the cyclin-dependent kinases involved in the control of the cell division cycle). Some kinases are misregulated in various human pathologies, including cancers. Using a specialized screening approach, chemical libraries were analysed, using on-site facilities at Roscoff, in order to identify small chemical inhibitors of protein kinases. Eight chemical scaffolds produced by marine organisms were characterized as candidate drugs by our screening facility, some of which are being considered as chemical tools to pinpoint specific cellular functions of the targeted kinases. In this review, we describe our existing screening facilities and we discuss new perspectives related to marine bioprospecting.

Superior ophthalmic vein thrombosis is a rare entity, which may lead to serious vision complications. We report the unusual observation of a 78-year-old patient who developed exophtalmos, chemosis, and blurred vision due to isolated superior ophthalmic vein thrombosis. This rare complication is likely due to tamoxifen therapy. In contrast with published data, in the present case, cessation of tamoxifen therapy did not improve ocular symptoms.

The prevalence of chemotherapy-induced anemia in lung cancer is estimated at about 80%.

We report the case of a woman with an ALK positive lung adenocarcinoma, who developed bilateral complex renal cysts 17 months after the introduction of treatment with crizotinib. Clinical investigation led to the conclusion that the cysts were due to anticancer drug. Regression of the renal cysts was observed one month after cessation of the crizotinib. This case illustrates that specific and little known toxicities can occur with these novel molecules which have entered use for the management of lung cancer.

Eribulin gained its approval in March 2011 for the treatment of patients with locally advanced or metastatic breast cancer (MBC) whose disease has progressed despite anthracycline and taxane-containing regimens. This study retrospectively assessed the efficacy, safety and cost of this treatment for all patients with MBC treated by eribulin in Franche-Comté. Ninety-four patients received eribulin between July 2006 and October 2013. The median age was 62 years (35-83). Median overall survival was 10.3 months [95% CI: 7.6 to 17.9]. Median progression-free-survival was 3.8 months [95% CI: 2.9 to 5.0]. Clinical benefit was obtained in 55% evaluable patients [95% CI: 43.1 to 66.9] by RECIST criteria. Most common grade 3-4 adverse events (AEs) were neutropenia (38%), asthenia (10%) and peripheral neuropathy (7%). Median cost of the treatment was 9767 € per patient (6344-17,517). This analysis found similar results to the EMBRACE study despite less selected population. A medico-economic evaluation cost-utility type would assess the effectiveness of this strategy compared to standard treatments.

Two or three systematic intravitreal injections (IVT) may be prescribed in a PRN approach to treat an exudative recurrence of neovascular age-related macular degeneration (AMD), according to the phenotype. Optical coherence tomography (OCT) may be performed immediately before the 2nd or the 3rd scheduled IVT, making it possible to cancel the procedure in the absence of exudation. The aim of the study was to evaluate the usefulness of this OCT examination and to assess the percentage of IVT cancelled, in order to evaluate a potential medico-economic benefit.

The mortality rate for malignant melanoma is higher in elderly patients aged 75 years or more, with over 25% of melanomas being diagnosed in this population. This poorer prognosis might perhaps be improved by emerging targeted therapies and immunotherapy, although these agents must be prescribed with care in this rather fragile population. The purpose of our review of the literature concerning phase-2 and -3 published trials of these innovative molecules was to examine their optimal use in elderly patients presenting metastatic malignant melanoma. Most of the trials examined included elderly patients and some were analyzed by age sub-groups. In conclusion, elderly patients with ECOG 0/1 status can be given ipilimumab or vemurafenib as first-line therapy depending on tumoral BRaf mutation status. The benefit of combined targeted therapies does not seem to apply consistently in elderly patients and their use must be discussed. Further specific data must be collected in elderly patients concerning anti-PD1 molecules. For more fragile patients, risk scales or scores should enable more accurate use of innovative therapies in metastatic melanoma. Moreover, physicians must be aware of the common drug interactions with targeted therapies, since elderly patients are often taking several concomitant drugs.

Oncologic management in pediatric patient may be associated with a high risk of neurosensory deficit, such as taste, olfaction, vision and hearing. These neurosensory deficits can be linked to chemotherapy toxicity or to a direct deleterious effect of local radiotherapy or surgical management in case of craniofacial cancers. Neurosensory deficit may be temporary but are usually irreversible and frequently progress after the completion of treatment. Taste and olfaction deficits expose to high risk of nutritional complications and quality of life alteration. Hyposialia, as a result of irradiation of the salivary glands, increases taste changes and the risk of dental caries. The risk of cataract is present in patients who received high dose corticosteroids and/or brain or orbital irradiation. When hearing is affected, a risk of impaired intellectual or academic performance is increased with an impact on the quality of life in absence of specific care. Finally, there are some cosmetic consequences of therapy such as alopecia and scarring that alter the image of the patient. Early detection of these problems in order to limit medical, psychological, educational and social impact is mandatory. Moreover, high risk of worsening of these deficits after completion of therapy support long-term follow-up children treated for cancer, especially with head and neck primary.

Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.

Impaired renal function may occur following multimodal treatment of cancer in childhood. Renal late effects caused by chemotherapy, renal surgery and/or radiotherapy are now well described; but little is known about their prevalence and time of development. Herein, we provide a synthesis of the different renal complications that may occur with their physiopathology in relation with specific treatment exposures. This review summarized the literature that supported the recommendations issued by the long-term follow-up group of the "Société française des cancers de l'enfant (SFCE)" for childhood cancer survivors at risk for nephrotoxicity (www.sfce.org ; www.soc-nephrologie.org/SNP/index.htm). We developed these monitoring elements and the lifestyle recommendations for all asymptomatic survivors.

Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivor. The most clinically evident and best known cardiotoxicity is the anthracycline adverse effect with heart failure. Many cardiovascular adverse effects appear after cancer therapy: heart congestive failure, myocardial ischemia, hypertension, thromboembolic complications, arrhythmias and conduction disturbances. There are potential strategies to mitigate the risks of cardiac complications for cancer patients with physical examination, echocardiography and electrocardiogram. The management of the cardiotoxicity is variable.

Cure rates for most childhood cancers and adolescents have made remarkable progress over the last thirty to forty years. The development of secondary malignancies has become an important question for these patients. The frequency is low, but the risk is significantly higher (between 3 and 10 times) and it is the leading cause of long-term mortality off relapse. In this literature review, we discuss the epidemiological aspect and the risk factors contributing to this increased risk, and conclude with a summary of current recommendations for screening and surveillance. We also discuss briefly the constitutional predisposing genetic contributions to other cancers.