Search

MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS. Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma subtype. More than 80% of GIST are characterized by activating mutations in KIT or PDGFRA genes, but rare molecular subtypes exist. Localized GIST can be cured by surgery. Adjuvant treatment with imatinib is the gold standard in high-risk GIST presenting mutations sensitive to this tyrosine kinase inhibitor. The development of tyrosine kinase inhibitors targeting KIT and PDGFRA has revolutionized the prognosis of metastatic GIST, by increasing the median overall survival: from less than 18 months to more than 70 months within 20 years. Similary to other histological subtypes, the diagnostic and therapeutic management of GIST must be referred to sarcoma reference centers., Competing Interests: S. Watson déclare avoir participé à des interventions ponctuelles pour Deciphera, Amgen, AstraZeneca et avoir été prise en charge, à l’occasion de déplacements pour congrès, par Amgen, PharmaMar, Deciphera. C. Bonnet déclare avoir participé à des interventions ponctuelles pour GSK et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Amgen.

Sarcoma consists in a group of rare malignant tumours of mesenchymal origin characterized by their vast clinical, pathological and biological heterogeneity. The pathological diagnosis of sarcoma relies classically of the differentiation features of tumour cells, with dozens of different tumour subtypes described in the last international classifications. Over the last decades, the advances in the development of new techniques of molecular biology have led to a major complexification of sarcoma classification, with the identification of multiple and specific molecular alterations that have led to significant changes for patients diagnostic, prognostic and therapeutic management. This review aims at giving an overview on the current knowledge of the molecular biology of soft tissue sarcoma, and emphasizes on their consequences for the daily management of patients., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: This study aimed to examine the vulnerability of Francophone single mothers at risk of homelessness in Northern Ontario. The project also endeavoured to document the quest for autonomy of these women in a minority context., Method: Employing a qualitative approach, eleven life stories were obtained from five women. Although none were homeless at the time of the interviews, in terms of living on the street, two were living with friends and the others were at risk of becoming homeless. All of the participants were between 20 and 59 years old and had completed their secondary education., Results: Taking into account their economic and social situation, as well as the participants' health and cultural resources, vulnerabilities throughout the life course were analyzed., Conclusion: The life trajectory of these women showed us that their significant vulnerabilities are relative to the amount of autonomy they are able to secure through the services provided by supporting agencies, particularly in a linguistic minority context. In addition, the triple stigmatization (economic, linguistic and gender relations) requires a broader understanding of the resilience of these women in their journey from poverty (economic) to social (and linguistic) exclusion, and vulnerability. Despite these challenges, each of the individuals interviewed in this study, for whom the quest for autonomy is a continual struggle, demonstrated resilience.

The MET tyrosine-kinase receptor is implicated in embryonic development and tissue repair. It appears to be a key of tumour development since it drives cell migration and invasion and can induce the conversion from an epithelial to a mesenchymal phenotype. Aberrant signaling of the MET pathways is associated with an aggressive prognosis and a poor outcome. Preliminary clinical results of several MET inhibitors have been encouraging particularly in tumours in which MET was amplified or mutated. MET inhibition could be especially interesting in association with others drugs since activation of MET is a secondary event induced by hypoxia, inflammatory cytokines or HER inhibitors that could exacerbate the malignant properties of transformed cells. Molecular targeted therapies against MET could therefore be effective as a combination approach.

It has long been known that the hedgehog signaling pathway is crucial for embryonic development, in both Drosophila and vertebrate systems. During the past few years its implication in carcinogenesis has become clear and today it is acknowledged that this pathway plays a role in the malignant transformation of multiple cell types, either owing to the mutation of some of its components or to its erratic activation. New molecular targeted therapies that inhibit the pathway have shown their unquestionable efficiency in several tumours -among which basal cell carcinoma, medulloblastoma, or pancreatic adenocarcinoma. The assessment of these inhibitors in other types of tumours is currently underway with promising results, suggesting that the Sonic hedgehog signalling pathway may become one of the therapeutic targets of the future.