trial that contains Koo J, Wu X, Mao Z, Khuri FR, Sun SY. 2007;67:11712–20. Eur J Cancer. are trial that contains are In conclusion, the dysregulation of mTORC2 components and downstream effectors is increasingly emerging as a common finding across tumor types. Jia W, Sanders AJ, Jia G, Liu X, Lu R, Jiang WG. RICTOR Amplification and ovarian carcinoma as inclusion criteria, 1 is phase 1/phase 2 (1 open) [5]. In a recent study of lung neuroendocrine tumors comprising different histological subtypes, RICTOR copy number gains were found in 23.6% of cases (26). open and 0 Sci Signal. Zou Z, Chen J, Yang J, Bai X. Retrospective studies performed in colorectal cancer (CRC) showed higher RICTOR mRNA and protein expression levels compared with adjacent tissues, with an undefined impact on patients’ prognosis (45,46). Search our clinical trials database for all cancer trials and studies recruiting in the UK, Questions about cancer? Terms and Conditions, Systemic Mastocytosis With An Associated Hematological Neoplasm (SM-AHN) 2007;19:117–23. mTORC2 is defined by its scaffold protein RICTOR and promotes the stability and activation of AKT, SGK and PKC. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used). trial that contains Hresko RC, Mueckler M. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. The lack of this complex feedback loop in the presence of dual mTORC1/2 targeting agents evidently limits potential clinical benefit obtainable instead from mTORC2-specific inhibition. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. AKT signaling activated RAC1 through the RAC-GEF TIAM1, while PKC signaling dampened expression of the endogenous RAC1 inhibitor, RHOGDI2 [57]. [24] Therefore, the influence of RICTOR and mTORC2 on Akt signaling has been associated with insulin resistance and type 2 diabetes. closed. CGH, comparative genomic hybridization; CGP, comprehensive genomic profile; CNG, copy number gain; CNV, copy number variation; DSS, disease-specific survival; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; NE, neuroendocrine; NOS, not otherwise specified; NR, not reported; PDAC, pancreatic ductal carcinoma; Ref, reference; RFS, relapse free survival; RT-PCR, reverse transcriptase PCR; SNP, single nucleotide polymorphism; TGCA, The Cancer Genome Atlas; WES, whole exon sequencing; WB, western-blot. AKT activates downstream signals involved in cell proliferation, differentiation, survival and migration. McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI, Cassidy J, McLeod HL. RICTOR Amplification is an inclusion criterion in 1 clinical trial RICTOR Amplification is an inclusion criterion in 2 clinical trials This clinical benefit prompted in vitro and in vivo experiments that demonstrated the sensitivity of RICTOR-amplified non-small-cell lung cancer cell lines to both dual mTORC1/2 inhibitors and RICTOR genetic silencing, suggesting the potential role of Rictor as a druggable target (24). Huang PH. Here, we discuss the biology of RICTOR in tumor and the prospects of targeting RICTOR as a complementary therapy to inhibit RTK co-activation. RICTOR International Cancer Genome Consortium.Summary of gene and mutations by cancer type from ICGC, RICTOR Cancer Genome Anatomy Project, NCIGene Summary, RICTOR COSMIC, Sanger InstituteSomatic mutation information and related details. MiR-424/503-mediated Rictor upregulation promotes tumor progression. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, et al. Although there is concordance among studies that this site is not mandatory for mTORC2 complex assembly, it still remains controversial whether the Thr1135 phosphorylation exerts a regulatory role or is dispensable for modulation of mTORC2 kinase activity (12,13). Dev Cell. You can read more about the curation process here. Epidermis-specific deletion of RICTOR prior to a protocol of chemical-induced carcinogenesis resulted in the reduction of skin tumor incidence (38%) compared with control groups (100%) (76). Activation of the PI3K/AKT/mTOR signaling pathway is associated with growth and progression of colorectal cancer (CRC). RICTOR Amplification and desmoid-type fibromatosis as inclusion criteria, 1 is phase 1/phase 2 (1 open) [5]. RICTOR is altered in 3.18% of non-small cell lung carcinoma patients The aforementioned clinical trials applied NGS and Nanostring for copy number variation detection and IHC for assessment of Rictor protein levels. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells [25]. Interestingly in a cell line combining RICTOR and PDGFR amplification, RICTOR knockdown was associated with significantly reduced proliferation in vitro and in vivo, consistent with RICTOR’s role as an oncogenic driver downstream of PDGFR [26]. Deptor, DEP domain containing mTOR-interacting protein; GRp58, 58 kDa glucose-regulated protein; Hsp70, heat shock protein 70; IKK, IκB kinase; NBS1, Nijmegen breakage syndrome protein 1; mSin1, mammalian stress activated protein kinase interacting protein 1; PRAS40, proline-rich Akt substrate of 40 kDa; Protor, protein observed with Rictor; Rac1, Ras-related C3 botulinum toxin substrate 1; Raptor, regulatory associated protein of mTOR; Rictor, rapamycin-insensitive companion of mTOR; Tel2, telomerase maintenance 2; Tti1, Tel2-interacting protein 1; XPLN, exchange factor found in platelets, leukemic and neuronal tissues. RICTOR is altered in 4.38% of neuroendocrine carcinoma patients Garcia-Martinez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. A more extensive correlation between mTORC2-RICTOR aberrations and survival outcomes from large datasets (i.e. Several preclinical data suggested that Rictor might be part of other protein complexes that do not include mTOR itself or other mTORC2 components. 2003;17:590–603. RICTOR, Cancer Genetics Web: http://www.cancer-genetics.org/RICTOR.htm Accessed: This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.Note: content of abstracts copyright of respective publishers - seek permission where appropriate. are 2010;12:675–84. Neoplasia. trial that contains Moreover, co-silencing of mTORC2/RICTOR and EGFR increased the sensitivity to commonly used anti-GBM chemotherapy in cell lines and eradicated the tumor in in vivo models, highlighting the urgent need for the development of a selective mTORC2–Rictor inhibitor for single or combinatorial treatment (38,57,59). 5. trial that contains Of the Of the Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. RICTOR is altered in 4.6% of urothelial carcinoma patients Graph generated 01 September 2019 using data from, Tag cloud generated 01 September, 2019 using data from, Creative Commons Attribution-ShareAlike 4.0 International License, RICTOR; RPTOR independent companion of MTOR complex 2, RICTOR and MTOR (FRAP1; MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004 [PubMed 15268862]).

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