[Cancer pain therapy: beyond conventional pharmacological approaches]. / Traitement de la douleur cancéreuse : au-delà des approches médicamenteuses conventionnelles.

Pain management in oncology is evolving progressively thanks to integrative approaches. In accordance with the type of pain and patient specifics, treatment possibilities are thus multiplied by combining conventional pharmacology, interventional approaches, physical and psychological treatments as well as complementary medicines, in a holistic perspective. International Societies Guidelines and scientific literature lend their support to such treatment plans. This article covers a number of interventional treatments and complementary options that are available. Their relevance is all the more important in view of the necessity to limit secondary effects and long-term opioids, especially in cancer survivors.

La prise en charge de la douleur en oncologie s'enrichit progressivement grâce à une approche intégrative. Celle-ci permet d'élargir la palette des outils thérapeutiques du praticien en combinant, selon les caractéristiques de la douleur et les spécificités du patient, les approches conventionnelles et complémentaires dans une vision holistique du patient. Les recommandations des sociétés internationales et la littérature scientifique s'étayent dans cette direction. Cet article couvre une partie des thérapies interventionnelles et des options complémentaires possibles. Leur pertinence est d'autant plus grande dans l'optique de limiter les effets secondaires des traitements médicamenteux et les opioïdes au long cours, prioritairement chez les patients en rémission ou avec une maladie contrôlée.

Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells.

The anaplastic lymphoma kinase (ALK) gene is overexpressed, mutated or amplified in most neuroblastoma (NB), a pediatric neural crest-derived embryonal tumor. The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process. However, the precise role of activating ALK mutations or ALK-wt overexpression in NB tumor initiation needs further clarification. Human ALK-wt, ALK-F1174L, or ALK-R1275Q were stably expressed in murine neural crest progenitor cells (NCPC), MONC-1 or JoMa1, immortalized with v-Myc or Tamoxifen-inducible Myc-ERT, respectively. While orthotopic implantations of MONC- 1 parental cells in nude mice generated various tumor types, such as NB, osteo/ chondrosarcoma, and undifferentiated tumors, due to v-Myc oncogenic activity, MONC-1-ALK-F1174L cells only produced undifferentiated tumors. Furthermore, our data represent the first demonstration of ALK-wt transforming capacity, as ALK-wt expression in JoMa1 cells, likewise ALK-F1174L, or ALK-R1275Q, in absence of exogenous Myc-ERT activity, was sufficient to induce the formation of aggressive and undifferentiated neural crest cell-derived tumors, but not to drive NB development. Interestingly, JoMa1-ALK tumors and their derived cell lines upregulated Myc endogenous expression, resulting from ALK activation, and both ALK and Myc activities were necessary to confer tumorigenic properties on tumor-derived JoMa1 cells in vitro.