Advances in the field of GIST accumulate very rapidly. The objective of this short review is to underline their consequences for the diagnostic practice and for the understanding of their pathogenesis. The diagnosis of GIST still relies on histology and immunohistochemistry; this is only in the case of the very rare KIT-negative tumors that other markers (such as DOG-1 and PKCtheta) have to be considered and that the identification of mutations of KIT et PDGRA may have a diagnostic interest. A new prognostic classification of GIST has been proposed: it acknowledges the existence of truly benign GISTs and is adapted to the primary site of the lesion in order to underline the usually better prognosis of gastric GISTs. The search for mutations of KIT et PDGRA must be done in specialized laboratories. It is important for the evaluation of the sensivity to imatinib, and to the other targeted therapies which may find a role in the treatment of advanced tumors, especially of imatinib-resistent GISTs. Much remains to be done in order to decipher the molecular mechanisms responsible for tumor progression in GISTs: their knowledge will be important to validate new prognostic markers.

Colorectal cancer remains one of the major causes of cancer death. Recent identification of new molecular targets led to the development of novel agents directed against growth factor receptors or key factors of angiogenesis. Recent phase III trials demonstrated a significant clinical benefit with bevacizumab, a VEGF inhibitor, and with EGFR-inhibitors, namely cetuximab and panitumumab. In this article we review the diverse treatment options combining cytotoxic and targeted therapies available for patients with metastatic colorectal cancer.

Xeroderma pigmentosum is a rare and severe photodermatitis without cure. Skin cancers are inevitable and give rise to iterative skin resections often mutilating especially in the face. We report the case of two sisters suffering from severe forms of xeroderma pigmentosum. Given the rapid emergence of multicancerous lesions, we opted for a radical approach entailing successively all aesthetic sub-units of the face. The reconstruction uses an original method used initially in the great burned: the artificial dermis. This simple method, providing a quality sub-soil, has helped us in these two complex cases to ensure coverage of a large defect providing a tissue recovery of excellent trophic and aesthetics quality. Thanks to this treatment strategy, we were able to significantly delay the development of this disease. With a retreat of 35 months, the quality of reconstruction by artificial dermis is considered to be satisfactory for its elasticity and its trophicity.

In the adjuvant setting, whole breast radiation therapy (RT) delivering 50 Gy in 5 weeks with or without a boost to the tumor bed remains the standard of care. RT indications and volume definition are generally dependant on existing prognostic factors. Except in particular cases, RT technique does not vary according to the patient or tumor biology profiles in terms of total dose, dose per fraction, fractionation, and RT duration. The challenge is to define new parameters or tumor biology profiles that will allow patient selection for more tailored RT than the 5 to 7 week standard schedules. The future issue is to define biological markers able to screen patients and tumors according to their high metastatic potential (in which the primary therapeutic challenge may not be locoregional control) and those patients that have a particular radiosensitivity to ionizing radiation for higher benefit/risk ratio. Thus, it is probable that patient profiles, tumor biology markers and gene expression profiling could provide in future an added value to conventional markers to predict patients at high-risk of local and distant recurrences who need tailored treatment or a particular sequence of adjuvant therapy.

During last decade, many progresses have been made in the understanding of thyroid cancer molecular biology. This knowledge led to the development of novel targeted therapy in iodine-resistant patients. However, the management of patients remains complex because of the broad spectrum of clinical presentation of thyroid cancers, differences in their natural histories and the lack of data about randomized trials. Angiogenesis inhibitors (sorafenib, motesanib, axitinib and vandetanib) have shown promising activity in differentiated thyroid cancer. Vandetanib, an inhibitor of RET and VEGFR tyrosine-kinases, is promising in medullary thyroid cancers. Preliminary results of these trials are discussed in this review.

This review article presents the improvements made in the field of molecular biology in oncology and their diagnostic and therapeutic consequences. As an illustration, three types of tumors for which these projections strongly modified the management will be used as a basis in this article: breast cancer, kidney cancer and colorectal cancer. Indeed, the last years, new prognostic factors (natural evolution of a specific patient's tumor) and predictive factors (prediction of the responsiveness to anticancer therapies) have emerged for these tumors. In addition, a better comprehension of the mechanisms implied in the development of cancers allowed the advent of many molecular-targeted therapies, which constitute a true revolution in oncology.

The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. Its inactivation has an inhibitory effect on the growth and spread of the tumoral cells. It therefore represents an attractive target to treat different cancers. Several molecules have already been registered while others are still under evaluation. One of the common side effects of these therapies is the development of cutaneous toxicities, more precisely a cutaneous rash, sometimes major and distressing. The physiopathology of these cutaneous side effects is poorly understood. Moreover a correlation between the severity of the rash and the tumoral response has been demonstrated in some studies. If this link is confirmed, the rash could be used as a marker for the anti-tumoral activity. This review will summarize the clinical presentations and the current recommendations for the management of cutaneous toxicities induced by EGFR inhibitors.

L-asparaginase is commonly used in the chemotherapy regimens for acute lymphoblastic leukaemia. Its use is associated with thrombotic complications in 1 to 14 % of the cases. The pathogenesis of this complication is still unclear. However, the decrease of antithrombin seems to play an important role. We report a case of a 17-year old man with a acute lymphoblastic leukaemia, who developed a cerebral sinovenous thrombosis due to an acquired deficiency of antithrombin and protein C and S following L-asparaginase chemotherapy. We discuss the use of prophylactic supplements of antithrombin and the value of screening of thrombophilia based on the recent medical literature.

Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic diseases. Hematological disorders associated with hypereosinophilias can be classified as clonal, reactive or idiopathic, and recently the improvements of cytogenetic, molecular biology and immunology have allowed to revisit numerous cases previously diagnosed as idiopathic hypereosinophilic syndrome. Reactive eosinophilias are mainly associated with lymphoma or abnormal, often clonal T lymphoid population. Clonal eosinophilia is related either to various myeloid malignancies or to a genuine myeloproliferative disorder from the eosinophile lineage, the so-called chronic eosinophilic leukaemia. Chronic eosinophilic leukaemia can be associated with recurrent genes rearrangements involving PDGFRA, PDGFRB and FGFR1 or with clonal abnormalities not yet categorized. Idiopathic hypereosinophilic syndrome remains an exclusive diagnosis in presence of moderate or severe unexplained eosinophilia with target organ damage. The purpose of the diagnostic work-up of hypereosinophilic syndrome is to evidence either an abnormal T cell population or a clonal haematopoiesis. Imatinib mesylate dramatically improves chronic eosinophilic leukaemias associated with PDGFR abnormalities, while corticosteroids are still the main treatment for the other patients. In a near future, advances could arise from identification of new genes involved in clonal eosinophilia or in alternative therapy such as the anti-IL-5 antibodies.

Tumor cells exhibit significant variations in the rate of pro- or anti-tumoral proteins that provide them a selective advantage of growth over normal cells. The control of these rates occurs at the three DNA, RNA and protein levels, and is determined by the structure of each of these three actors for the implementation of the molecular mechanisms involved in the control of the synthesis, maturation and stability of the mRNA and the protein itself. We give here an overview of the main events that can lead to a disruption of these mechanisms.

Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to defective cell cycle control and genomic instability due to the impaired repair of DNA double strand breaks. Although increased radiosensitivity in ATM heterozygous patients has been suggested in preclinical data, clinical implication of ATM variant remains debated. Despite frequent in vitro hypersensitivity in patients with severe radiation-induced delayed toxicity, heterozygoty for ATM gene does not represent the major cause of unexpected complications after radiation therapy. This might be partially due to potential coexistence of alterations in additional genes that would play a role in development of late radiation-induced adverse response. Although several data suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis at lower doses compared with patients who did not possess these genetic alterations, the relationship between the presence of ATM mutations or sequence variants and radiation-induced toxicity remains controversial in part because of their biological and functional significance. Considering the lack of prospective data, patients with ATM mutation should be considered as candidates for both dose volume and dose reduction clinical trials.

The preclinical rationale for chemoradiation was demonstrated. While chemoradiation allowed for improved outcome in nonsmall cell lung cancer patients, prognosis of patients remains particularly pejorative, encouraging major expansion of targeted therapies concurrently with radiotherapy. Thorough knowledge in biological mechanisms of oncogenesis permitted identifying new therapeutic targets, for which specific interactions allow pharmacological radiosensitivity modulation. Two modalities of EGFR inhibitors have been developed: monoclonal antibodies and tyrosin kinase inhibitors, which assessement remains at its beginning. Angiogenesis inhibition was also developed, illustrating the absolute necessity for careful clinical assessment. Drugs with multiple targets are becoming available and offer new optimization modalities for radiation therapy.

We characterized the successive and cumulative molecular modifications associated with transition in the histological stages of lung squamous carcinogenesis (normal epithelium from smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive carcinoma) to improve our understanding of the mechanisms involved and identify new biomarkers for the early detection of lung squamous cell carcinoma. We employed immunohistochemistry, immunofluorescence, gene expression microarrays and quantitative RT-PCR to successively assess the expression of various proteins involved in cellular proliferation and apoptosis as well as messenger RNAs and microRNAs expression. Based on our data, we have improved the classification of bronchial preneoplastic lesions and furthered our understanding of the pathways involved in early lung carcinogenesis. The large number of biomarkers highlighted in these studies has opened two major and interesting perspectives: 1) the development of non invasive tests based on biomarkers for lung cancer detection at pre-invasive and early invasive stages and 2) new avenues of fundamental research whose goal is to understand the mechanisms underlying lung carcinogenesis.

P53 is 30. Even if the tumor suppressor functions of p53 have long been recognized, the cancer-killing activity of p53 has not yet been exploited selectively and efficiently in the clinic. Recent genetic studies in mice identified MDM2 and MDMX as key regulators of p53 and as such as specific chemotherapeutic targets for treatment of cancer. Specific MDM2 and MDMX antagonists are now being developed as tools to unleash p53 activity in various tumors.