Pancreatic cancer, mostly represented by pancreatic ductal adenocarcinoma, is a major public health burden in developed countries. More than half a million people are expected to die from pancreatic cancer, worldwide, in 2030. Age and tobacco are the main identified risk factors in sporadic cases, when many genetic syndromes increase the risk significantly. History of pancreatic cancer is a significant risk factor for pancreatic cancer for any first-degree related individual, known as familial pancreatic cancer. The genetic signature of this syndrome is probably due to a still not identified autosomal dominantly inherited gene with reduced penetrance. The risk increases with the number of first-degree relatives involved. Precursor lesions are known to give rise to invasive pancreatic cancer. These particular lesions are either macroscopic (intraductal papillary mucinous neoplasia and mucinous cystic neoplasms), or microscopic (pancreatic intraepithelial neoplasia). It is possible to identify a orouo of hig h-risk individuals who could be candidate for screening.

Deregulation of FGF (fibroblast growth factor)/FGFR (fibroblast growth factor receptor) signalling leads to the promotion of several oncogenic mechanisms: proliferation, epithelial-mesenchymal transition, cytoskeleton modifications, migration and angiogenesis. Deregulation of this pathway is reported in various cancers at early stages, and can therefore be responsible for the emergence of the hallmarks of cancer. It is necessary to precise downstream pathways of FGFR signalling to understand its oncogenic potential. We will then describe its implications in different cancer types. Oncogenic mechanisms will be studied through the example of melanoma, in which deregulation of FGF/FGFR pathway is considered as a driver event and occurs in nearly 90% of cases. The FGF/FGFR signalling pathway is a putative therapeutic target. Numerous agents are in active development, operating through a selective or multi-targeted approach. Recent studies have shown rather disappointing results in non-selected patients, but promising results in patients with FGF/FGFR pathway alterations. A careful screening of patients is the key to a valuable evaluation of these new targeted molecular therapies.

Primary aldostéronism (PA) is the most frequent form of arterial hypertension. It is caused in the majority of cases by an aldosterone producing adenoma (APA) of the adrenal cortex or by bilateral adrenal hyperplasia. Recent advances have allowed to identify a certain number of genetic abnormalities involved in the development of APA or responsible for familial forms of PA. These findings have highlighted the central role of calcium signaling in this process. In this review we will discuss the genetic defects associated with PA and discuss the mechanisms whereby they lead to increased aldosterone production and cell proliferation. The possible consequences that this knowledge will have on the diagnosis and management of PA will be addressed.

Planning a pregnancy for patients with a history of cancer, including breast cancer, is a clinical situation that becomes more and more common. Several specific items are to be discussed: decrease of fertility after cancer treatment, fertility preservation options, impact of pregnancy on cancer recurrence risk and appropriate interval between cancer and pregnancy. Programming pregnancy after cancer is doable in a multidisciplinary setting, and begins at cancer diagnosis to anticipate the various specific pitfalls. Favor adequate oncologic care remains the leading rule.

This article presents a bibliometric study carried out in order to describe the trends and evolutions of French breast cancer research from 2003 to 2013. The results show an increase in the number of publications, especially international publications coordinated by non-French institutions. The most visible topics, in terms of number of publications by keywords, are related to biology, clinical trials and genetics. Most publications are written by authors affiliated to comprehensive cancer centres, followed by universities, research centres, university hospitals and governmental agencies. The importance of publications by topic varies throughout the years: there has been an increase of the number of publications related to targeted therapies or genomics. The importance of institutions or country affiliation of authors varies with the topics. This study, especially the analysis by keywords, enables the coordinators of research programs to identify the predominant actors and themes.

The deficiency of mismatch repair system is one of the main pathways in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2, MSH6 and PMS2. Colorectal cancer develops in the majority of cases from precancerous lesions called adenomas. Only few studies have reported on the deficiencies of these proteins in adenomas.

Philadelphia or BCR-ABL positive acute lymphoblastic leukemia (PH+ ALL) is the most common and severe of adult ALL. The only potentially curator treatment remains allogeneic hematopoietic stem cells transplantation (SCT) in first complete remission. The use of imatinib has revolutionized the treatment of chronic myeloid leukemia. Its incorporation into PH + ALL protocols also improved the prognosis of this disease giving better complete remission rates compared to chemotherapy alone. The treatment of patients not eligible for SCT remains controversial. Prolonged use of high dose tyrosine kinase inhibitors (TKI) (ie: imatinib at 600 or 800 mg/j) as maintenance therapy seems to be a reasonable approach. We present a case of prolonged molecular remission of PH+ ALL under TKI alone as maintenance therapy.

The identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib. Two phase III trials demonstrated crizotinib efficacy in second line metastatic (PROFILE 1007) and more recently first line metastatic (PROFILE 1014) NSCLC in terms of progression-free survival and also objective response. However, within 12 to 16 months, patients will progress due to the emergence of acquired resistance mechanisms such as mutation (L1196M) or amplification of the ALK gene, as well as activation of alternative signaling pathways (EGFR, KRAS). Second generation ALK inhibitors have been developed such as ceritinib, alectinib, and AP26113. This review will present those new drugs, summarize the results of their ongoing trials, and discuss the best way to treat ALK+ NSCLC patients.

Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI. The median progression-free survival (PFS) increased from 3.2 to 7.8 months in patients receiving everolimus and exemestane compared to placebo and exemestane. The magnitude of benefit was consistent in all pre-specified subgroups. Side effects were manageable and the quality of life was at least maintained. Everolimus has also beenrecently studied in HER2 positive locally advanced or metastatic disease in heavily pretreated patients (BOLERO 3 trial). This trial met its primary endpoint. The median PFS was increased in patients receiving trastuzumab, vinorelbine and everolimus compared to patients receiving trastuzumab, vinorelbine and placebo. We review pharmacological data and side effects of the drug. We also review the most important clinical trials leading to reimbursement of everolimus in metastatic breast cancer.

Miliary brain metastases are a rare form of brain metastatic lesions.

Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology.

Metastatic melanoma has been a very poor prognostic cancer with a median of survival between six to eight months. A lot of new therapies have been discovered these last years. Two types of treatment have emerged: immunotherapy and targeted therapy. Targeted therapies have been developed because of the discovery of new oncogenic mutations with a big impact of melanoma development. The efficacy is great with a high overall response and a good tolerance. However, most of patients escape in few months of targeted therapy. The sequence of drug using and their combination are the question for the next years.

Metastatic melanoma treatment has been radically modified over the last four years with the emergence of new and effective therapeutic strategies targeted anti-BRAF therapies as well as immunotherapy. Following this latter immunotherapy strategy, anti-CTLA4 antibody ipilimumab demonstrated a benefit in terms of overall survival in patients with metastatic melanoma and is now challenged by other checkpoint inhibitors, antibodies directed against PD-1 and PD-L1 that have extremely promising benefit/risk ratio. Adverse events as well as evaluation criteria are different from the ones associated with classical chemotherapy or targeted therapies. The challenge for the next years will be to optimize these new strategies, by possibly using these new drugs sequentially or in combination for a higher clinical benefit for our patients.

High rates of early colorectal cancers (CRC) are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now no molecular studies have been performed in the Tunisian population.