Abstract: The present invention relates to a compound ABT-263 or a derivative thereof for use in the treatment of uveal melanoma and/or uveal melanoma resistant. Inventors provide evidence that ABT-263 displays clear antiproliferative and proapoptotic activities in metastatic uveal melanoma cells both in vitro and in vivo. They also demonstrated that ABT-263 effect is accompanied with the activation of the ER stress response pathway that exerts cytoprotective effect. Blocking ER stress enhanced ABT-263 killing efficacy. The combination of ABT-263 with PERK inhibition synergistically reduced the survival rate of primary uveal melanoma cells.

Abstract: Here, in multi-scale analyses using single-cell RNA sequencing of six different primary uveal melanomas, inventors uncover a previously unrecognized intratumor heterogeneity at the genetic and transcriptomic level. They identify distinct transcriptional cell states and diverse tumor-associated populations in a subset of primary uveal melanomas.

Abstract: Here, in multi-scale analyses using single-cell RNA sequencing of six different primary uveal melanomas, inventors uncover a previously unrecognized intratumor heterogeneity at the genetic and transcriptomic level. They identify distinct transcriptional cell states and diversetumor-associated populations in a subset of primary uveal melanomas. They also decipher a gene regulatory network underlying an invasive and poor prognosis state driven in part by the transcription factor HES6, a member of the NOTCH signaling pathway. HES6 heterogenous expression has been validated by RNAscope assays within primary uveal melanomas, which unveils the existence of these cells conveying a dismal prognosis in tumors diagnosed with a favorable outcome using bulk analyses. Depletion of HES6 impairs growth, migration and metastatic dissemination, demonstrating essential roles of HES6 in uveal melanoma progression.

Abstract: The present invention relates to a method for treating a subject suffering from melanoma resistant by administering to said subject an inhibitor of NAMPT. Using a global metabolic profiling, inventors have showed that in addition to glycolysis, the BRAF inhibitor, PLX4032, promoted a complex metabolic rewiring of melanoma cells, including protein catabolism and fatty acid synthesis. Importantly, they observed that PLX4032 reduced the levels of nicotinamide adenine dinucleotide (NAD+), an important redox co-factor in numerous metabolic processes, including glycolysis, tricarboxylic acid cycle (TCA) cycle, glutamate metabolism and fatty acid betaoxidation. Pharmacological or genetic inhibition of NAMPT impaired melanoma cell growth, whereas the overexpression of NAMPT dampened the antiproliferative effect of PLX4032. In vivo, the inhibition of NAMPT also prevented the xenograft development of PLX4032-sensitive and -resistant melanoma cells, identifying NAMPT as a potential target for BRAFi-resistant melanomas.

Abstract: The present invention relates to a mutant of MITF which is useful as a marker for predisposition to the development of cancer and to uses thereof in diagnosis and preventive treatments, sumoylation being reduced or absent in this mutant.

Abstract: The invention relates to the field of oncology and to chemotherapy resistance and relapse. Thus the invention provides compositions and methods for inhibiting tumorigenicity of senescent cancer cells induced by a chemotherapeutic agent. The invention also provides compositions and methods for inhibiting conversion of non-stem cancer cells (non-CSCs) into tumor initiating cancer stem cells (CSCs) induced by a chemotherapeutic agent.

Abstract: The present invention relates to products and compositions containing (i) a chemotherapeutic agent and (ii) at least an active compound chosen from CCL2 inhibitors, CCR2 inhibitors, NF-?B inhibitors, PARP-1 inhibitors and ATM inhibitors, as a combined preparation for simultaneous, separate or sequential use for inhibiting tumor development caused by tumor cell senescence induced by said chemotherapeutic agent. The invention also refers to a method for monitoring the response to a chemotherapeutic agent of a patient suffering from a cancer, and to a method for predicting the tumor size evolution and/or the onset of metastasis in a patient suffering from a cancer.

Abstract: The present invention relates to a mutant of MITF which is useful as a marker for predisposition to the development of cancer and to uses thereof in diagnosis and preventive treatments, sumoylation being reduced or absent in this mutant.