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DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress. High levels of DDIT4 were significantly associated with a worse prognosis in acute myeloid leukemia, breast cancer, glioblastoma multiforme, colon, skin and lung cancer. Conversely, a high DDIT4 expression was associated with an improved prognostic in gastric cancer. DDIT4 was not associated with the outcome of ovarian cancers. Analysis with data from the Cell Miner Tool in 60 cancer cell lines indicated that although rapamycin activity was correlated with levels of MTOR, it is not influenced by DDIT4 expression. In summary, DDIT4 might serve as a novel prognostic biomarker in several malignancies. DDIT4 activity could be responsible for resistance to mTOR inhibitors and is a potential candidate for the development of targeted therapy.DDIT4 gene (for DNA-damage-inducible transcript 4), also known as REDD1 or RTP801, encodes a protein product that is induced by a variety of stress conditions and whose major function is to inhibit mTORC1 by stabilizing the TSC1-TSC2 inhibitory complex [1][2][3] .Despite inhibition of mTOR pathway is a current strategy in the treatment of cancer, paradoxically, several in vitro and in vivo studies indicate that DDIT4 have a protective role against apoptosis, where a knockdown of this gene lead to increased levels of dexamethasone-induced cell death in murine lymphocytes without effect in glucocorticoid-induced cell death in primary thymocytes 4,5 .A recent study by Celik et al., reported that DDIT4 may be used as a surrogate pharmacodynamic marker of ezrin inhibitors compound activity 6 . Only two previous reports describe the prognostic value of DDIT4. Jia et al. 7 , evaluated DDIT4 protein expression (assessed by immunohistochemistry) in 100 primary ovarian tumors describing that a high DDIT4 expression is related to a shorter disease-free survival (P = 0.020) and overall survival (P = 0.023) 7 . In the other hand, our group screened 449 genes related with triple negative breast cancer aggressiveness and found that a high DDIT4 expression was an independent factor associated with a shorter

The CARIATIDE study was designed to assess the impact of educational materials (EMs) on compliance and persistence rates with aromatase inhibitor (AI) treatment in postmenopausal women with hormone-receptor-positive early breast cancer. Patients were randomized to standard AI treatment (Group A; N = 1379) or standard AI treatment plus EMs containing information on a range of breast-cancer-related topics (Group B; N = 1379). Standardized questionnaires assessed investigator-perceived levels of care and evaluated patient compliance and behavior. At 1 year, there was no significant difference in compliance between Group A and Group B (81% vs. 82%, p = 0.4524). However, higher compliance in patients receiving EMs was observed in Sweden/Finland (p = 0.0246). Compliance with initial AI and persistence rate were not significantly altered by EM. Other factors associated with improved compliance, irrespective of EMs, e.g. administration of chemotherapy were identified.

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