fenretinide

Summary

Summary: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.

Top Publications

  1. Sabichi A, Xu H, Fischer S, Zou C, Yang X, Steele V, et al. Retinoid receptor-dependent and independent biological activities of novel fenretinide analogues and metabolites. Clin Cancer Res. 2003;9:4606-13 pubmed
    b>Fenretinide (4-HPR) is a retinoid analogue with antitumor and chemopreventive activities...
  2. Cuperus R, Tytgat G, Leen R, Brites P, Bras J, Caron H, et al. Pleiotropic effects of fenretinide in neuroblastoma cell lines and multicellular tumor spheroids. Int J Oncol. 2008;32:1011-9 pubmed
    The efficacy and mechanism of action of fenretinide (4-HPR), a vitamin A analogue, was investigated in a panel of six neuroblastoma cell lines and multicellular tumor spheroids...
  3. Lim S, Gutierrez Puente Y, Tari A. N-(4-hydroxyphenyl)-retinamide selectively increases All-TRANS retinoic acid inhibitory effects in HER2/NEU-overexpressing breast cancer cells. Tumour Biol. 2002;23:279-86 pubmed
    ..Combining 4HPR with ATRA may lead to a novel, selective therapeutic or chemopreventive strategy against HER2/NEU-overexpressing breast tumors. ..
  4. Kutty R, Samuel W, Jaworski C, Duncan T, Nagineni C, Raghavachari N, et al. MicroRNA expression in human retinal pigment epithelial (ARPE-19) cells: increased expression of microRNA-9 by N-(4-hydroxyphenyl)retinamide. Mol Vis. 2010;16:1475-86 pubmed
    ..Several miRNAs with inherent ability to regulate cell growth, differentiation and development are also normally expressed in ARPE-19 cells. Thus, miR-9 and other miRNAs could be important in maintaining RPE cell function. ..
  5. Fang H, Harned T, Kalous O, Maldonado V, DeClerck Y, Reynolds C. Synergistic activity of fenretinide and the Bcl-2 family protein inhibitor ABT-737 against human neuroblastoma. Clin Cancer Res. 2011;17:7093-104 pubmed publisher
    b>Fenretinide (4-HPR) is a cytotoxic retinoid with minimal systemic toxicity that has shown clinical activity against recurrent high-risk neuroblastoma...
  6. Gopal A, Pagel J, Hedin N, Press O. Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism. Blood. 2004;103:3516-20 pubmed
    ..the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo...
  7. Lovat P, Oliverio S, Corazzari M, Ranalli M, Pearson A, Melino G, et al. Induction of GADD153 and Bak: novel molecular targets of fenretinide-induced apoptosis of neuroblastoma. Cancer Lett. 2003;197:157-63 pubmed
    Unlike 13-cis retinoic acid, the synthetic retinoid fenretinide induces apoptosis of neuroblastoma cells and in vitro acts synergistically with the chemotherapeutic drugs, cisplatin, etoposide and carboplatin...
  8. Kadara H, Tahara E, Kim H, Lotan D, Myers J, Lotan R. Involvement of Rac in fenretinide-induced apoptosis. Cancer Res. 2008;68:4416-23 pubmed publisher
    ..These findings show a preferential susceptibility of metastatic cells to the proapoptotic retinoid 4HPR through Rac activation and support the use of ROS-inducing agents such as 4HPR against metastatic cancer cells. ..
  9. Rahmaniyan M, Curley R, Obeid L, Hannun Y, Kraveka J. Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide. J Biol Chem. 2011;286:24754-64 pubmed publisher
    ..We previously demonstrated that fenretinide (4-HPR) inhibited DES activity in SMS-KCNR neuroblastoma cells...

More Information

Publications100

  1. Yang H, Zhan Q, Wan Y. Enrichment of Nur77 mediated by retinoic acid receptor ? leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors. Hepatology. 2011;53:865-74 pubmed publisher
    The synthetic retinoid fenretinide is one of the most promising clinically tested retinoids...
  2. Zhang H, Mi J, Fang H, Wang Z, Wang C, Wu L, et al. Preferential eradication of acute myelogenous leukemia stem cells by fenretinide. Proc Natl Acad Sci U S A. 2013;110:5606-11 pubmed publisher
    ..Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/..
  3. Simeone A, Tari A. How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci. 2004;61:1475-84 pubmed
    ..retinoic acid, 9-cis-retinoic acid, LGD1069 (Targretin, bexarotene), and N-(4-hydroxyphenyl)retinamide (fenretinide) as breast cancer chemopreventive agents is being studied...
  4. Lovat P, Oliverio S, Ranalli M, Corazzari M, Rodolfo C, Bernassola F, et al. GADD153 and 12-lipoxygenase mediate fenretinide-induced apoptosis of neuroblastoma. Cancer Res. 2002;62:5158-67 pubmed
    The synthetic retinoid fenretinide induces apoptosis of neuroblastoma cells and in vitro acts synergistically with chemotherapeutic drugs used to treat neuroblastoma...
  5. William W, Lee J, Lippman S, Martin J, Chakravarti N, Tran H, et al. High-dose fenretinide in oral leukoplakia. Cancer Prev Res (Phila). 2009;2:22-6 pubmed publisher
    We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor-independent ..
  6. Cuello M, Coats A, Darko I, Ettenberg S, Gardner G, Nau M, et al. N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines. Cell Death Differ. 2004;11:527-41 pubmed
    ..These findings offer a promising and novel strategy for the treatment of ovarian cancer. ..
  7. Shishodia S, Gutierrez A, Lotan R, Aggarwal B. N-(4-hydroxyphenyl)retinamide inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of I(kappa)B(alpha) kinase and nuclear factor-kappaB-regulated gene products. Cancer Res. 2005;65:9555-65 pubmed
    ..This correlated with potentiation of apoptosis induced by TNF and chemotherapeutic agents. ..
  8. Morales M, Perez Yarza G, Rementería N, Boyano M, Apraiz A, Gomez Munoz A, et al. 4-HPR-mediated leukemia cell cytotoxicity is triggered by ceramide-induced mitochondrial oxidative stress and is regulated downstream by Bcl-2. Free Radic Res. 2007;41:591-601 pubmed
  9. Appierto V, Villani M, Cavadini E, Gariboldi M, De Cecco L, Pierotti M, et al. Analysis of gene expression identifies PLAB as a mediator of the apoptotic activity of fenretinide in human ovarian cancer cells. Oncogene. 2007;26:3952-62 pubmed
    b>Fenretinide (4-HPR) is a synthetic retinoid with antitumor activity, which induces apoptosis in cancer cell lines of different histotypes...
  10. Okuda T, Kawakami S, Higuchi Y, Satoh T, Oka Y, Yokoyama M, et al. Enhanced in vivo antitumor efficacy of fenretinide encapsulated in polymeric micelles. Int J Pharm. 2009;373:100-6 pubmed publisher
    b>Fenretinide (N-(4-hydroxyphenyl)retinamide, 4-HPR) is a synthetic retinoid with high antitumor activity against a variety of malignant cells in vitro, and is a promising candidate for cancer chemoprevention and chemotherapy...
  11. Kerl K, Ries D, Unland R, Borchert C, Moreno N, Hasselblatt M, et al. The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells. BMC Cancer. 2013;13:286 pubmed publisher
    ..Rhabdoid tumors are highly aggressive malignancies affecting infants and very young children. In many instances these tumors are resistant to conventional type chemotherapy necessitating alternative approaches...
  12. Favoni R, de Cupis A, Bruno S, Yee D, Ferrera A, Pirani P, et al. Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines. Br J Cancer. 1998;77:2138-47 pubmed
    ..These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR. ..
  13. Guilbault C, De Sanctis J, Wojewodka G, Saeed Z, Lachance C, Skinner T, et al. Fenretinide corrects newly found ceramide deficiency in cystic fibrosis. Am J Respir Cell Mol Biol. 2008;38:47-56 pubmed
    ..Since it has been previously reported that in vitro treatment with fenretinide induced ceramide in neuroblastoma cell lines, we decided to test this drug in vivo using our Cftr-knockout mice ..
  14. Vilela R, Lands L, Meehan B, Kubow S. Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following pre-treatment with fenretinide. Int Immunopharmacol. 2006;6:1651-64 pubmed
    ..As fenretinide is a ceramide up-regulating drug that inhibits the activation of the pro-inflammatory transcriptional factor, ..
  15. Serrano D, Gandini S, Mariani L, Bonanni B, Santinelli A, Guerrieri Gonzaga A, et al. Computer-assisted image analysis of breast fine needle aspiration in a randomized chemoprevention trial of fenretinide vs. placebo in HRT users. Breast. 2008;17:91-7 pubmed
    ..women were randomized to oral (CEE) or transdermal (E2) estrogen replacement therapy (ERT) in association with fenretinide or placebo...
  16. Lovat P, Di Sano F, Corazzari M, Fazi B, Donnorso R, Pearson A, et al. Gangliosides link the acidic sphingomyelinase-mediated induction of ceramide to 12-lipoxygenase-dependent apoptosis of neuroblastoma in response to fenretinide. J Natl Cancer Inst. 2004;96:1288-99 pubmed
    ..b>Fenretinide, a retinoic acid derivative, is thought to induce apoptosis via increases in ceramide levels, but the link ..
  17. Wu J, DiPietrantonio A, Hsieh T. Mechanism of fenretinide (4-HPR)-induced cell death. Apoptosis. 2001;6:377-88 pubmed
    4-HPR (fenretinide) is a synthetic analog of retinoic acid (RA) whose potential as a chemopreventative agent has gained support from in vitro and animal experiments and in limited clinical trials...
  18. Wang H, Maurer B, Reynolds C, Cabot M. N-(4-hydroxyphenyl)retinamide elevates ceramide in neuroblastoma cell lines by coordinate activation of serine palmitoyltransferase and ceramide synthase. Cancer Res. 2001;61:5102-5 pubmed
    The retinoid N-(4-hydroxyphenyl)retinamide (4-HPR; fenretinide) is cytotoxic to a variety of cancer cell lines, and we previously showed an association between ceramide generation and 4-HPR cytotoxicity for neuroblastoma cell lines (B. J...
  19. Kraveka J, Li L, Szulc Z, Bielawski J, Ogretmen B, Hannun Y, et al. Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. J Biol Chem. 2007;282:16718-28 pubmed
    ..Additionally, we found that treatment of SMS-KCNR cells with fenretinide inhibited desaturase activity in a dose-dependent manner...
  20. Decensi A, Robertson C, Guerrieri Gonzaga A, Serrano D, Cazzaniga M, Mora S, et al. Randomized double-blind 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in high-risk premenopausal women. J Clin Oncol. 2009;27:3749-56 pubmed publisher
    Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial...
  21. Wang H, Maurer B, Liu Y, Wang E, Allegood J, Kelly S, et al. N-(4-Hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell killing. Mol Cancer Ther. 2008;7:2967-76 pubmed publisher
    b>Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is cytotoxic in many cancer cell types. Studies have shown that elevation of ceramide species plays a role in 4-HPR cytotoxicity...
  22. Eun S, Woo I, Jang H, Jin H, Kim M, Kim H, et al. Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening. Biochem Biophys Res Commun. 2008;373:58-63 pubmed publisher
  23. Sun S, Yue P, Lotan R. Induction of apoptosis by N-(4-hydroxyphenyl)retinamide and its association with reactive oxygen species, nuclear retinoic acid receptors, and apoptosis-related genes in human prostate carcinoma cells. Mol Pharmacol. 1999;55:403-10 pubmed
    ..Furthermore, 4HPR modulated the expression levels of some apoptosis-related gene (p21, c-myc, and c-jun), which may also contribute to the induction of apoptosis by 4HPR in HPC cells. ..
  24. Villani M, Appierto V, Cavadini E, Valsecchi M, Sonnino S, Curley R, et al. Identification of the fenretinide metabolite 4-oxo-fenretinide present in human plasma and formed in human ovarian carcinoma cells through induction of cytochrome P450 26A1. Clin Cancer Res. 2004;10:6265-75 pubmed
    The synthetic retinoid fenretinide (4-HPR) exhibits preventive and therapeutic activity against ovarian tumors...
  25. Takahashi N, Watanabe Y, Maitani Y, Yamauchi T, Higashiyama K, Ohba T. p-Dodecylaminophenol derived from the synthetic retinoid, fenretinide: antitumor efficacy in vitro and in vivo against human prostate cancer and mechanism of action. Int J Cancer. 2008;122:689-98 pubmed
    b>Fenretinide, N-(4-hydroxyphenyl)retinamide (4-HPR) is an aminophenol-containing synthetic retinoid derivative of all-trans-retinoic acid, which is a potent chemopreventive and antiproliferative agent against various cancers...
  26. Ponthan F, Lindskog M, Karnehed N, Castro J, Kogner P. Evaluation of anti-tumour effects of oral fenretinide (4-HPR) in rats with human neuroblastoma xenografts. Oncol Rep. 2003;10:1587-92 pubmed
    ..b>Fenretinide [N-(4-hydroxyphenyl)retinamide] has been identified as a synthetic retinoid able to induce apoptosis of ..
  27. Holmes W, Soprano D, Soprano K. Elucidation of molecular events mediating induction of apoptosis by synthetic retinoids using a CD437-resistant ovarian carcinoma cell line. J Biol Chem. 2002;277:45408-19 pubmed
    ..by tumor necrosis factor-alpha but not resistant to the induction of apoptosis by another synthetic retinoid, fenretinide N-(4-hydroxyphenyl)retinamide...
  28. Decensi A, Torrisi R, Gozza A, Severi G, Bertelli G, Fontana V, et al. Effect of fenretinide on bone mineral density and metabolism in women with early breast cancer. Breast Cancer Res Treat. 1999;53:145-51 pubmed
    ..We studied the effects of the synthetic retinoid fenretinide (N-4-hydroxyphenylretinamide, or 4-HPR) administered for a mean of 40 months on bone mineral density and ..
  29. O Donnell P, Guo W, Reynolds C, Maurer B. N-(4-hydroxyphenyl)retinamide increases ceramide and is cytotoxic to acute lymphoblastic leukemia cell lines, but not to non-malignant lymphocytes. Leukemia. 2002;16:902-10 pubmed
    ..Thus, 4-HPR was cytotoxic and increased ceramide in ALL cell lines, but not in non-malignant lymphoid cell types. ..
  30. Appierto V, Tiberio P, Villani M, Cavadini E, Formelli F. PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation. Carcinogenesis. 2009;30:824-31 pubmed publisher
    b>Fenretinide [N-(4-hydroxyphenyl)-retinamide (4HPR)] is a synthetic retinoid with antitumor activity that induces apoptosis in various types of cancer cell...
  31. Hail N, Kim H, Lotan R. Mechanisms of fenretinide-induced apoptosis. Apoptosis. 2006;11:1677-94 pubmed
    b>Fenretinide, a synthetic retinoid, has emerged as a promising anticancer agent based on numerous in vitro and animal studies, as well as chemoprevention clinical trials...
  32. Damodar Reddy C, Guttapalli A, Adamson P, Vemuri M, O ROURKE D, Sutton L, et al. Anticancer effects of fenretinide in human medulloblastoma. Cancer Lett. 2006;231:262-9 pubmed
    N-(4-hydroxyphenyl) retinamide (4-HPR, fenretinide) a synthetic retinoid is in clinical trials for the treatment of several malignancies...
  33. Hu Y, Liu H, He Y, Fang Y, Fang J, Wan Y. Transcriptome profiling and genome-wide DNA binding define the differential role of fenretinide and all-trans RA in regulating the death and survival of human hepatocellular carcinoma Huh7 cells. Biochem Pharmacol. 2013;85:1007-17 pubmed publisher
    b>Fenretinide is significantly more effective in inducing apoptosis in cancer cells than all-trans retinoic acid (ATRA)...
  34. Sogno I, Vené R, Ferrari N, De Censi A, Imperatori A, Noonan D, et al. Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies. Crit Rev Oncol Hematol. 2010;75:2-14 pubmed publisher
    Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent...
  35. Armstrong J, Martin S, Illingworth N, Jamieson D, Neilson A, Lovat P, et al. The impact of retinoic acid treatment on the sensitivity of neuroblastoma cells to fenretinide. Oncol Rep. 2012;27:293-8 pubmed publisher
    ..A retinoid analogue, fenretinide [N-(4-hydroxyphenyl) retinamide; 4-HPR] can induce apoptosis in neuroblastoma cell lines and could ..
  36. Benelli R, Monteghirfo S, Vené R, Tosetti F, Ferrari N. The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3beta pathway and beta-catenin stability. Mol Cancer. 2010;9:142 pubmed publisher
    ..These data point to 4HPR as a negative regulator of AKT phosphorylation, effectively targeting the beta-catenin pathway and inducing a relatively benign phenotype in prostate cancer cells, limiting neoangiogenesis and cell invasion. ..
  37. Lopez Vales R, Redensek A, Skinner T, Rathore K, Ghasemlou N, Wojewodka G, et al. Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice. J Neurosci. 2010;30:3220-6 pubmed publisher
    ..We show here that daily oral administration of fenretinide after spinal cord contusion injury led to a significant decrease in AA and an increase in DHA levels in plasma ..
  38. Simeone A, Ekmekcioglu S, Broemeling L, Grimm E, Tari A. A novel mechanism by which N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell growth: the production of nitric oxide. Mol Cancer Ther. 2002;1:1009-17 pubmed
    ..When combined with 4-HPR, IFN-gamma and TAM enhanced NOSII expression. Thus, we have identified a novel mechanism by which 4-HPR induces apoptosis in breast cancer cells, i.e., by increasing NOS expression to induce NO production. ..
  39. Vratilova J, Frgala T, Maurer B, Patrick Reynolds C. Liquid chromatography method for quantifying N-(4-hydroxyphenyl)retinamide and N-(4-methoxyphenyl)retinamide in tissues. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;808:125-30 pubmed
    ..liquid chromatography (HPLC) method was developed to measure levels of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its main metabolite N-(4-methoxyphenyl)retinamide (4-MPR) in tissue...
  40. Chiesa F, Tradati N, Grigolato R, Boracchi P, Biganzoli E, Crose N, et al. Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results. Int J Cancer. 2005;115:625-9 pubmed
    We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia...
  41. Chen S, Samuel W, Fariss R, Duncan T, Kutty R, Wiggert B. Differentiation of human retinal pigment epithelial cells into neuronal phenotype by N-(4-hydroxyphenyl)retinamide. J Neurochem. 2003;84:972-81 pubmed
    ..Here, we report the novel finding that N-(4-hydroxyphenyl)retinamide (fenretinide), a synthetic retinoic acid derivative and a potential chemopreventive agent against cancer, induced the ..
  42. Pirkmaier A, Yuen K, Hendley J, O Connell M, Germain D. Cyclin d1 overexpression sensitizes breast cancer cells to fenretinide. Clin Cancer Res. 2003;9:1877-84 pubmed
    b>Fenretinide has shown promise in the chemoprevention of breast cancer, a tumor type in which the oncogene cyclin D1 is overexpressed frequently...
  43. Garaventa A, Luksch R, Lo Piccolo M, Cavadini E, Montaldo P, Pizzitola M, et al. Phase I trial and pharmacokinetics of fenretinide in children with neuroblastoma. Clin Cancer Res. 2003;9:2032-9 pubmed
    b>Fenretinide (4HPR), a synthetic retinoid, induces apoptosis in neuroblastoma cells. A Phase I study in children with neuroblastoma was designed to determine maximum tolerated dose, toxicity, and pharmacokinetics...
  44. Veronesi U, Mariani L, Decensi A, Formelli F, Camerini T, Miceli R, et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol. 2006;17:1065-71 pubmed
    The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women...
  45. Goto H, Takahashi H, Fujii H, Ikuta K, Yokota S. N-(4-Hydroxyphenyl)retinamide (4-HPR) induces leukemia cell death via generation of reactive oxygen species. Int J Hematol. 2003;78:219-25 pubmed
    ..Our findings suggest that ROS play a significant role in the antileukemia effect of 4-HPR and that the glutathione level in leukemias may be associated the sensitivity of the cells to 4-HPR. ..
  46. Cuperus R, Leen R, Tytgat G, Caron H, van Kuilenburg A. Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma. Cell Mol Life Sci. 2010;67:807-16 pubmed publisher
    b>Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines...
  47. Simeone A, Deng C, Kelloff G, Steele V, Johnson M, Tari A. N-(4-Hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells. Carcinogenesis. 2005;26:1000-7 pubmed
    ..These in vitro results suggest that 4-HPR may be an effective chemopreventive agent against breast tumors that exhibit BRCA1 mutations because of its ability to induce NO-mediated apoptosis in such tumors. ..
  48. Ribatti D, Alessandri G, Baronio M, Raffaghello L, Cosimo E, Marimpietri D, et al. Inhibition of neuroblastoma-induced angiogenesis by fenretinide. Int J Cancer. 2001;94:314-21 pubmed
    ..The synthetic retinoid fenretinide (HPR) inhibits carcinogenesis in various animal models...
  49. Maurer B, Kalous O, Yesair D, Wu X, Janeba J, Maldonado V, et al. Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Clin Cancer Res. 2007;13:3079-86 pubmed
    b>Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule...
  50. Dmitrovsky E. Fenretinide activates a distinct apoptotic pathway. J Natl Cancer Inst. 2004;96:1264-5 pubmed
  51. Simeone A, Li Y, Broemeling L, Johnson M, Tuna M, Tari A. Cyclooxygenase-2 is essential for HER2/neu to suppress N- (4-hydroxyphenyl)retinamide apoptotic effects in breast cancer cells. Cancer Res. 2004;64:1224-8 pubmed
    ..Combining 4-HPR with COX-2 inhibitors may be a novel chemopreventive strategy against HER2/neu-overexpressing breast tumors. ..
  52. Um S, Kwon Y, Han H, Park S, Park M, Rho Y, et al. Synthesis and biological activity of novel retinamide and retinoate derivatives. Chem Pharm Bull (Tokyo). 2004;52:501-6 pubmed
    ..These data may delineate the relationship between the structure and function of retinoate and retinamide derivatives. ..
  53. Kang M, Wan Z, Kang Y, Sposto R, Reynolds C. Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation. J Natl Cancer Inst. 2008;100:580-95 pubmed publisher
    ..An increase of Mcl-1 protein in response to ABT-737 is one mechanism of ABT-737 resistance that can be overcome by 4-HPR, resulting in synergistic cytotoxicity of ABT-737 combined with 4-HPR in ALL cell lines. ..
  54. Hewson Q, Lovat P, Corazzari M, Catterall J, Redfern C. The NF-kappaB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Apoptosis. 2005;10:493-8 pubmed
    b>Fenretinide induces apoptosis in SH-SY5Y neuroblastoma cells via a signaling pathway involving the production of reactive oxygen species (ROS), 12-lipoxygenase activity and the induction of the GADD153 transcription factor...
  55. Um S, Lee S, Kim E, Han H, Koh Y, Hong K, et al. Antiproliferative mechanism of retinoid derivatives in ovarian cancer cells. Cancer Lett. 2001;174:127-34 pubmed
    ..Taken together coupled with its selective activity only for RARgamma, these results suggest that 4-HPR could be less toxic, and very effective anticancer drugs for late stage ovarian cancer. ..
  56. Puduvalli V, Yung W, Hess K, Kuhn J, Groves M, Levin V, et al. Phase II study of fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American Brain Tumor Consortium study. J Clin Oncol. 2004;22:4282-9 pubmed
    b>Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas...
  57. Camerini T, Mariani L, De Palo G, Marubini E, Di Mauro M, Decensi A, et al. Safety of the synthetic retinoid fenretinide: long-term results from a controlled clinical trial for the prevention of contralateral breast cancer. J Clin Oncol. 2001;19:1664-70 pubmed
    To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention...
  58. Kouhara J, Yoshida T, Nakata S, Horinaka M, Wakada M, Ueda Y, et al. Fenretinide up-regulates DR5/TRAIL-R2 expression via the induction of the transcription factor CHOP and combined treatment with fenretinide and TRAIL induces synergistic apoptosis in colon cancer cell lines. Int J Oncol. 2007;30:679-87 pubmed
    b>Fenretinide (N-[4-Hydroxyphenyl]retinamide; 4HPR) is a semisynthetic retinoid that induces apoptosis in a variety of malignancies. Fenretinide has been examined in clinical trials as a cancer chemopreventive and chemotherapeutic agent...
  59. Armstrong J, Veal G, Redfern C, Lovat P. Role of Noxa in p53-independent fenretinide-induced apoptosis of neuroectodermal tumours. Apoptosis. 2007;12:613-22 pubmed
    b>Fenretinide-induced apoptosis of neuroectodermal tumour cells is mediated through generation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, mitochondrial cytochrome c release and caspase activation...
  60. Bikman B, Guan Y, Shui G, Siddique M, Holland W, Kim J, et al. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. J Biol Chem. 2012;287:17426-37 pubmed publisher
    b>Fenretinide is a synthetic retinoid that is being tested in clinical trials for the treatment of breast cancer and insulin resistance, but its mechanism of action has been elusive...
  61. Holpuch A, Phelps M, Desai K, Chen W, Koutras G, Han B, et al. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention. Carcinogenesis. 2012;33:1098-105 pubmed publisher
    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels...
  62. Bu P, Wan Y. Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor beta dependent. BMC Cancer. 2007;7:236 pubmed publisher
    ..chromatin immunoprecipitation (ChIP) were conducted to evaluate the activation of RXRalpha/RARbeta pathway by fenretinide. Knockdown of RARbeta mRNA expression was achieved by siRNA transfection...
  63. Sreekumar P, Zhou J, Sohn J, Spee C, Ryan S, Maurer B, et al. N-(4-hydroxyphenyl) retinamide augments laser-induced choroidal neovascularization in mice. Invest Ophthalmol Vis Sci. 2008;49:1210-20 pubmed publisher
    ..Consistent with the preferential loss of RPE in CNV lesions in vivo, 4-HPR induces apoptosis of nonpolarized RPE in the presence of serum. ..
  64. Wei J, Whiteford C, Cenacchi N, Son C, Khan J. BBC3 mediates fenretinide-induced cell death in neuroblastoma. Oncogene. 2005;24:7976-83 pubmed
    b>Fenretinide (4-HPR) is a synthetic retinoid whose apoptosis-inducing effects have been demonstrated in many tumor types. The precise mechanism of its apoptotic action is not fully understood...
  65. Illingworth N, Boddy A, Daly A, Veal G. Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP-glucuronosyltransferases. Br J Pharmacol. 2011;162:989-99 pubmed publisher
    b>Fenretinide (4-HPR) is a retinoic acid analogue, currently used in clinical trials in oncology...
  66. Tiwari M, Kumar A, Sinha R, Shrivastava A, Balapure A, Sharma R, et al. Mechanism of 4-HPR-induced apoptosis in glioma cells: evidences suggesting role of mitochondrial-mediated pathway and endoplasmic reticulum stress. Carcinogenesis. 2006;27:2047-58 pubmed
    ..Taken together, these results suggest the role of mitochondrial-mediated pathway and ER stress as a key event in 4-HPR-induced apoptosis in glioma cells. ..
  67. Sabichi A, Modiano M, Lee J, PENG Y, Xu M, Villar H, et al. Breast tissue accumulation of retinamides in a randomized short-term study of fenretinide. Clin Cancer Res. 2003;9:2400-5 pubmed
    The synthetic retinoid N-(4-hydroxyphenyl)retinamide [4-HPR (or fenretinide)] has preclinical and clinical preventive activity in breast carcinogenesis...
  68. Formelli F, Camerini T, Cavadini E, Appierto V, Villani M, Costa A, et al. Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome. Cancer Epidemiol Biomarkers Prev. 2003;12:34-41 pubmed
    To assess, in women participating in a breast cancer prevention trialon fenretinide (4-HPR), the relationship of drug and retinol levels with the risk of second breast malignancy, taking into account age and menopausal status...
  69. Urban D, Myers R, Manne U, Weiss H, Mohler J, Perkins D, et al. Evaluation of biomarker modulation by fenretinide in prostate cancer patients. Eur Urol. 1999;35:429-38 pubmed
    ..Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given. ..
  70. Raguenez G, Mühlethaler Mottet A, Meier R, Duros C, Benard J, Gross N. Fenretinide-induced caspase-8 activation and apoptosis in an established model of metastatic neuroblastoma. BMC Cancer. 2009;9:97 pubmed publisher
    ..For some patients, an adjuvant retinoid therapy is proposed, such as the synthetic retinoid fenretinide (4-HPR), an apoptotic inducer...
  71. Woo I, Eun S, Jang H, Kang E, Kim G, Kim H, et al. Identification of ADP-ribosylation factor 4 as a suppressor of N-(4-hydroxyphenyl)retinamide-induced cell death. Cancer Lett. 2009;276:53-60 pubmed publisher
    ..Our results suggest that ARF4 participates in the regulation of glioblastoma apoptosis through the inhibition of stress-mediated apoptotic signals. ..
  72. Fontana J, Rishi A. Classical and novel retinoids: their targets in cancer therapy. Leukemia. 2002;16:463-72 pubmed
    ..Both 4-HPR and CD437/AHPN display significant potential as therapeutic agents in the treatment of a number of premalignant and malignant conditions. ..
  73. Park J, Liu L, Kim I, Kim J, You K, Kim D. Identification of the genes involved in enhanced fenretinide-induced apoptosis by parthenolide in human hepatoma cells. Cancer Res. 2005;65:2804-14 pubmed
    b>Fenretinide (N-4-hydroxyphenyl retinamide, 4HPR) is a synthetic anticancer retinoid that is a well-known apoptosis-inducing agent...
  74. Samuel W, Kutty R, Sekhar S, Vijayasarathy C, Wiggert B, Redmond T. Mitogen-activated protein kinase pathway mediates N-(4-hydroxyphenyl)retinamide-induced neuronal differentiation in the ARPE-19 human retinal pigment epithelial cell line. J Neurochem. 2008;106:591-602 pubmed publisher
    We have shown previously that N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide), a retinoic acid derivative, induces neuronal differentiation in cultured human retinal pigment epithelial (RPE) cells [Chen et al., J. Neurochem...
  75. Lee J, Nguyen V, Chen M, Adamson P. A rapid, sensitive and selective liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for determination of fenretinide (4-HPR) in plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;862:64-71 pubmed
    ..LC-MS/MS) method using an atmospheric pressure chemical ionization source (APCI) for the quantification of fenretinide (4-HPR) in mouse plasma was developed and validated...
  76. Sun S, Li W, Yue P, Lippman S, Hong W, Lotan R. Mediation of N-(4-hydoxyphenyl)retinamide-induced apoptosis in human cancer cells by different mechanisms. Cancer Res. 1999;59:2493-8 pubmed
  77. Ferrari N, Pfeffer U, Dell eva R, Ambrosini C, Noonan D, Albini A. The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide. Clin Cancer Res. 2005;11:4610-9 pubmed
    Tumor growth appears to be an angiogenesis-dependent process. N-(4-hydroxyphenyl)retinamide (fenretinide; 4HPR) has been found to inhibit and/or prevent tumor growth under diverse conditions...
  78. White D, Burchill S. BAY 11-7082 induces cell death through NF-kappaB-independent mechanisms in the Ewing's sarcoma family of tumours. Cancer Lett. 2008;268:212-24 pubmed publisher
    The role of NF-kappaB in the Ewing's sarcoma family of tumours (ESFT) and their response to fenretinide has been investigated. Basal levels of phosphorylated NF-kappaB were low in all ESFT cells...
  79. Decensi A, Bonanni B, Baglietto L, Guerrieri Gonzaga A, Ramazzotto F, Johansson H, et al. A two-by-two factorial trial comparing oral with transdermal estrogen therapy and fenretinide with placebo on breast cancer biomarkers. Clin Cancer Res. 2004;10:4389-97 pubmed
    ..b>Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a ..
  80. Bonanni B, Lazzeroni M, Veronesi U. Synthetic retinoid fenretinide in breast cancer chemoprevention. Expert Rev Anticancer Ther. 2007;7:423-32 pubmed
    ..The induction of apoptosis is a unique feature of fenretinide, the most-studied retinoid in clinical trials of breast cancer chemoprevention, owing to its selective ..
  81. Myatt S, Redfern C, Burchill S. p38MAPK-Dependent sensitivity of Ewing's sarcoma family of tumors to fenretinide-induced cell death. Clin Cancer Res. 2005;11:3136-48 pubmed
    ..In this study, we have evaluated the effect of fenretinide [N-(4-hydroxyphenyl)retinamide] in ESFT models...
  82. Shimada K, Nakamura M, Ishida E, Kishi M, Yonehara S, Konishi N. Contributions of mitogen-activated protein kinase and nuclear factor kappa B to N-(4-hydroxyphenyl)retinamide-induced apoptosis in prostate cancer cells. Mol Carcinog. 2002;35:127-37 pubmed
    ..It thus appears that mitogen-activated protein kinase associated with the activity of NFkappaB plays an important role in the degree of resistance to 4-HPR-induced apoptosis in human prostate cancer cells. ..
  83. Torrisi R, Decensi A, Formelli F, Camerini T, De Palo G. Chemoprevention of breast cancer with fenretinide. Drugs. 2001;61:909-18 pubmed
    ..b>Fenretinide, the synthetic amide of retinoic acid, inhibits cell growth mostly through the induction of apoptosis with ..
  84. Puduvalli V, Li J, Chen L, McCutcheon I. Induction of apoptosis in primary meningioma cultures by fenretinide. Cancer Res. 2005;65:1547-53 pubmed
    b>Fenretinide, a synthetic retinoid that induces apoptosis in tumor cells in vitro, is being evaluated in clinical trials as a chemotherapeutic agent against several malignancies...
  85. Puduvalli V, Saito Y, Xu R, Kouraklis G, Levin V, Kyritsis A. Fenretinide activates caspases and induces apoptosis in gliomas. Clin Cancer Res. 1999;5:2230-5 pubmed
    The synthetic retinoid fenretinide (N-[4-hydroxyphenyl] retinamide or 4HPR) has been shown to not only inhibit cell growth but also to induce apoptosis in a variety of malignant cell lines...
  86. Maurer B, Kang M, Villablanca J, Janeba J, Groshen S, Matthay K, et al. Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: a report from the New Approaches to Neuroblastoma Therapy (NANT) consortium. Pediatr Blood Cancer. 2013;60:1801-8 pubmed publisher
    ..was conducted to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of fenretinide (4-HPR) delivered in an oral powderized lipid complex (LXS) in patients with relapsed/refractory neuroblastoma...
  87. Appierto V, Tiberio P, Cavadini E, Casalini P, Cappelletti G, Formelli F. Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth-inhibitory activity. Mol Cancer Ther. 2009;8:3360-8 pubmed publisher
    The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), a metabolite of fenretinide (4-HPR) present in plasma of 4-HPR-treated patients, is very effective in inducing growth inhibition and apoptosis in several cancer cell lines...
  88. Di Sano F, Fazi B, Citro G, Lovat P, Cesareni G, Piacentini M. Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells. Cancer Res. 2003;63:3860-5 pubmed
    ..In fact, overexpression of RTN-1C sensitizes CHP-100 cells to fenretinide-induced apoptosis...
  89. Zhu G, Cao X, Chang J, Milas L, Wallace S, Li C. Polymeric retinoid prodrug PG-4HPR enhances the radiation response of lung cancer. Oncol Rep. 2007;18:645-51 pubmed
    ..These results suggest that a polymeric delivery system may be useful for modulating radiosensitivity. ..
  90. Anding A, Chapman J, Barnett D, Curley R, Clagett Dame M. The unhydrolyzable fenretinide analogue 4-hydroxybenzylretinone induces the proapoptotic genes GADD153 (CHOP) and Bcl-2-binding component 3 (PUMA) and apoptosis that is caspase- dependent and independent of the retinoic acid receptor. Cancer Res. 2007;67:6270-7 pubmed
    ..These results suggest that a stress-mediated apoptotic cascade is involved in the mechanism of action of these retinoids. ..
  91. Lovat P, Corazzari M, Di Sano F, Piacentini M, Redfern C. The role of gangliosides in fenretinide-induced apoptosis of neuroblastoma. Cancer Lett. 2005;228:105-10 pubmed
    b>Fenretinide is thought to induce apoptosis via increases in ceramide levels but the mechanisms of ceramide generation and the link between ceramide and subsequent apoptosis in neuroblastoma cells is unclear...