Forward thinking does not seek to predict the future, to unveil it as if it were already in existence, rather, its aim is to help us to construct it. Although today's epidemiological and therapeutic situations for urogenital tumours can evolve over the next 10 years, diagnostic and therapeutic methods, as well as the treatment and implementation of innovations, are already rapidly changing. Rather than reducing our prospective thinking to the therapeutic treatment of cancer only, we will aim at proposing a global sanitary vision that includes diagnosis, therapies, prevention, routine utilisation of technomedicine, genomics and even nanomedicine. This journey into the near future of tomorrow's cancerology holds the promise of being better adapted to the evolution of the medical thinking process. Imagining the way we will be treating renal, prostatic and urothelial tumours in 10 years' time is as much an introspection into our present day treatment system as a projection into its hoped for future evolution.

Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage.

The acute lymphoblastic leukemia (ALL) is one of the first cancer for which emerged the particularity of the adolescent and young adult population. After decades of poorly concerted approaches, adult and pediatric haematologists found out that adolescents treated according to pediatric approaches had a better outcome than those treated in adult protocols. Therefore, pediatric-inspired therapies have been successfully implemented in the young adult population, leading to decreased criteria for allogeneic stem cell transplantation. More recently, a high prevalence of Philadelphia-like ALL has been identified in the AYA population, which opens the door to the combination of target therapy similar to Philadelphia-positive ALL. AYA patients require specific care programs including fertility counselling, adhesion evaluation, and long-term survivor follow-up. They are to be optimally treated by multidisciplinary teams, exploring their personal needs and determining the best management of the "whole patient".

Cabozantinib is an oral multiple tyrosine kinase receptor inhibitor (ITK): VEGFR2, c-MET and RET. Inhibition of VEGFR and c-MET decrease resistance of VEGFR inhibitor via c-MET axis. Cabozantinib improve progression-free survival (PFS) in progressive metastatic medullary thyroid cancer (MTC): 4 months in the placebo group and 11.2 months in the cabozantinib group (P<0.001) in all patient subgroups including those with or without prior ITK and RET mutation status. Cabozantinib increased overall survival (OS) compared with everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR ITK treatment: 21.4 months in cabozantinib group and 16.5 months in everolimus group (P<0.0003). Cabozantinib obtained the AMM for the treatment of progressive metastatic MTC and advanced renal cell carcinoma. Cabozantinib is a new option in the treatment of MTC by inclusion in therapeutic trials (no payment in this indication) and advanced renal cell carcinoma (hospital delivery). Its tolerance is similar to anti-angiogenic therapies and justifies an optimal management of the secondary effect.

Ground-glass opacities nodules are frequently detected with the advances of radiological imaging. These can be preinvasive lesions such as atypical adenomatous hyperplasia but also invasive lesions. It leads to question in patients with lung cancer about treatment strategy and follow up.

The search for mutations epidermal growth factor receptor (EGFR) has changed the therapeutic approach and prognosis of non-small cell lung cancer (NSCLC). The effectiveness of tyrosine kinase inhibitors (TKI) has been demonstrated orally in patients with EGFR mutation. We report the case of a patient for whom treatment with TKI was started effectively in a Critical Care Unit.

Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.

The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13.2) or without oxyphilia (Ch2q21), in association with a multinodular goiter (Ch14q32), or with a renal cancer (Ch1q21). Several candidate genes of susceptibility have been proposed: SRGAP1, NKX2-1, FOXE1 and HABP2. So far, it is considered that familial cases represent less than 5 % of thyroid cancers. Although rare, these cases represent a unique opportunity to improve our understanding of thyroid cancer. The identification of candidate genes will enrich our knowledge of thyroid cancer pathophysiology. Based on the literature and our experience of the follow-up of eight families with FNMTC, we discuss epidemiological, clinical, pathological and genetic aspects of FNMTC with a view to improve the diagnosis and treatment of this disease.

Lynch syndrome (LS) is a syndrome that carries a genetic predisposition to certain cancers associating, either in a single individual or in a family, a visceral tumour, mainly colorectal, with a high risk of other synchronous or metachronous cancers. LS is linked with mutations in the genes coding for proteins in the DNA repair system. Phenotypic variants of SL exist, including Muir-Torre syndrome (MTS) and Turcot syndrome (TS), both of which predispose to colorectal cancer. They may be distinguished by the presence of benign or malignant sebaceous tumours in MTS, and tumours of the central nervous system in TS.

ROS1 fusions are rare mutations that preferentially concern young and non-smoker women. The ROS1-rearranged protein conserves an intact tyrosine kinase domain, leading to the constitutive activation of the ROS1 tyrosine kinase function and of its downstream pathways, that are known to be involved in tumorigenesis. These molecular abnormalities have shown their oncogenic potential in animals' models and in human, with an early effect on carcinogenesis. Several partners have been identified. Patients with non-small cell lung cancers (NSCLC) harbouring ROS1 alterations can receive specific targeted therapies. Indeed, crizotinib has recently been approved in France in advanced ROS1-rearranged NSCLC. We propose a review of the oncogenic role of ROS1 rearrangements, the different methods for its diagnosis, and the available treatments.

Immune-checkpoint inhibitors represent potent new therapies for most lymphomas, particularly for refractory diseases. Contrasting with solid tumors the majority of lymphoma are sensitive to conventional therapies and immunotherapies such as anti-CD20 or anti-CD30. But relapsing lymphoma or refractory disease have a very poor prognosis and new drugs are mandatory. Immune-checkpoint inhibitors targeting CTLA4, PD-1 et PD-L1 demonstrated efficiency with prolonged survivals even after bone marrow allograft for aggressive disease. Lymphomas differ from solid tumors as tumor cells belong to the immune compartment and therefore molecules targeting immune cells may act on both immune environment and tumor cells. Furthermore, PD-L1 expression in most lymphomas is related to tumor cell molecular alterations such as PD-L1 gene amplification or mutation. PD-L1 protein expression on tumor cells and immune cells, particularly it frequency and distribution vary according to different lymphoma subtype and it may help to assess diagnosis as it may predict therapeutical response.

Theileria are obligate eukaryotic intracellular parasites of cattle. The diseases they cause, Tropical theileriosis and East Coast Fever, cause huge economic loss in East African, Mediterranean and central and South-East Asian countries. These apicomplexan parasites are the only intracellular eukaryotic parasites known to transform their host cell and represent a unique model to study host-parasite interactions and mechanisms of cancer onset.Here, we review how Theileria parasites induce transformation of their leukocyte host cell and discuss similarities with tumorigenesis. We describe how genomic innovation, epigenetic changes and hijacking of signal transductions enable a eukaryotic parasite to transform its host cell.

The remarkable efficacy of PD-1/PD-L1 and CTLA4 immune checkpoint inhibitors has led to numerous approvals in melanoma, non-small cell lung cancer, kidney cancer and several other cancers. Nevertheless, a response is observed in a variable proportion of patients, emphasizing the need for predictive biomarkers of efficacy of immune checkpoint inhibitors effectiveness. Several predictive biomarkers of efficacy are of interest: companion tests such PD-L1 immunohistochemistry, the mutational load, the immune status of the tumor and its molecular profile. They do not allow a perfect selection of the patients, but standardization procedures for certain techniques are ongoing. Moreover the emergence of new approaches, such as the multiplex in situ techniques and the microbiote analysis, may offer the opportunity to better select patients who really benefit from immunotherapy. The goal of this article is to discuss available and promising predictive biomarkers of efficacy for immunotherapy strategies.

The aim of this article is to emphasize the impact of the immune response in digestive cancers, especially from colorectal (CRC) origin. In this setting, an adaptive lymphocytic infiltrate underlines the prognostic impact of the immune response, because it is associated to a favorable outcome. The next challenge will be to validate, in a prospective therapeutic trial, the integration of the immune response as decisional parameter for adjuvant therapy. The immune response is also a predictive parameter in microsatellite instable metastatic CRC, characterized by an adaptive lymphocytic infiltrate, leading to a very high response rate to immune therapies. However, prognostic and predictive biomarkers still need to be optimized in order to better select patients. These data are also valuable for digestive non-colorectal cancers, which are briefly analyzed. The methodology for the assessment of these prognostic and predictive biomarkers, which represents an important issue in precision medicine, is also discussed.

Pre-mRNA splicing is an obligatory step required to assemble the vast majority of mRNAs in eukaryotes. In humans, each gene gives rise to at least two transcripts, with an average 6-8 spliced transcripts per gene. Pre-mRNA splicing is not unequivocal. Variations may occur, such that splicing can become alternative, thereby participating in increasing protein variability and restricting the gap that exists between the relatively low number of genes - between 20,000 and 25,000 in humans - and the much higher number of distinct proteins - at least 100,000. In addition, although alternative pre-mRNA splicing often fulfils cell-specific needs, many aberrant splicing events can happen and lead to either hereditary or acquired diseases such as neurodegenerative diseases or cancers. In those cases, alternative splicing events may serve as disease-associated markers, or even as targets for corrective approaches. In this review, we will summarize the main aspects of regulated alternative splicing. We will present the spliceosome, a large ribonucleoprotein complex that orchestrates the splicing reactions and that was recently identified as a preferential target for mutations in several pathologies. We shall discuss some spliceosome-associated defects linked to either cis (i.e on the DNA) or trans (e.g. in proteins) alterations of splicing machinery, like those that have been reported in genetic or acquired diseases.

Carcinomas are rare tumors of the adolescent-young adult (AYA) with a different spectrum from those of adults. The most common sites outside of the thyroid is the nasopharynx, salivary gland, colon-rectum and ovaries. If nasopharyngeal carcinoma or salivary gland tumors are good prognosis, others are more reserved prognosis, such as digestive carcinomas, gynecological or midline. The revelation modes are non-specific and depend on the location: mass, tumor syndrome, pain, impaired general condition. The unusual of pediatric carcinomas led to propose a systematic oncogenetic exploration. The medical history of the family, the symptoms and the type of the carcinoma should guide the analysis. In the absence of guidance, analysis of TP53 gene and, for carcinomas of the expanded spectrum of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, the search for mutation of MMR genes (mismatch repair) seems essential. Because of the rarity of these diseases and the absence of homogeneous recommendations, members of the rare tumors committee of the SFCE recommended for the management of these AJA, an histological review by a pathologist familiar with carcinomas of the adult, a double discussion between pediatric and adult oncologists, analysis of adult standards with adaptation to pediatric data, especially in terms of risk of side effects. An advice to a national opinion (by a member of FRACTURE group) or European (group EXPERT) is sometimes necessary in the most complex situations.