nach oben

Cancer Chemotherapy and Pharmacology

Erschienen in:

01.01.2010 | Mini Review

Bexarotene: a promising anticancer agent

verfasst von: Liyan Qu, Xiuwen Tang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Retinoids are biologically active derivatives of vitamin A, which play essential roles in embryonic or adult cell behavior modulating cell proliferation, differentiation and apoptosis. The biologic effects of retinoids are mediated by two distinct families of intracellular receptors: retinoid acid receptors (RARs)-α, -β and -γ and retinoid X receptors (RXR)-α, -β and -γ. Bexarotene is a selective RXR agonist, which exerts its effects in blocking cell cycle progression, inducing apoptosis and differentiation, preventing multidrug resistance, and inhibiting angiogenesis and metastasis, making it a promising chemopreventive agent against cancer.

Niederreither K, Subbarayan V, Dolle P, Chambon P (1999) Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet 21:346–347CrossRef

Lotan R (1996) Retinoids in cancer prevention. FASEB 10:1031–1039

Fanjul A, Dawson MI, Hobbs PD et al (1994) A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature 372:107–111CrossRefPubMed

Fenaux P, Chomienne C, Degos L (2001) All-trans retinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia. Semin Hematol 38(1):13–25CrossRefPubMed

Boehm MF, Zhang L, Badea BA et al (1994) Synthesis and structureactivity relationships of novel retinoid X receptor-selective retinoids. J Med Chem 37:2930–2941CrossRefPubMed

Dragnev KH, Rigas JR, Dmitrovsky E (2000) The retinoids and cancer prevention mechanisms. Oncologist 5:361–368CrossRefPubMed

Niles RM (2000) Recent advances in the use of vitamin A (retinoids) in the prevention and treatment of cancer. Nutrition 16:1084–1089CrossRefPubMed

Toma S, Raffo P, Isnardi L et al (1999) Retinoids in lung cancer chemoprevention and treatment. Ann Oncol 10:95–102CrossRef

Wong SF (2001) Oral bexarotene in the treatment of cutaneous T-cell lymphoma. Ann Pharmacother 35:1056–1065CrossRefPubMed

10.

Yocum RC, Miller VA, Warrell RP et al (2001) Long-term followup of patients with advanced non-small cell lung cancer treated with oral bexarotene. Proc Am Soc Clin Oncol 20:267

11.

Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R (2007) FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12:1247–1252CrossRefPubMed

12.

Blumenschein GR Jr, Khuri FR, von Pawel J et al (2008) Phase III trial comparing carboplatin, paclitaxel, and bexarotene with carboplatin and paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT II. J Clin Oncol 26:1879–1885CrossRefPubMed

13.

Tooker P, Yen WC, Ng SC et al (2007) Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res 67:4425–4433CrossRefPubMed

14.

Brown PH, Subbaramaiah K, Salmon AP et al (2008) Combination chemoprevention of HER2/neu-induced breast cancer using a cyclooxygenase-2 inhibitor and a retinoid X receptor-selective retinoid. Cancer Prev Res (Phila Pa) 1:208–214

15.

Zanardi S, Serrano D, Argusti A et al (2006) Clinical trials with retinoids for breast cancer chemoprevention. Endocr Relat Cancer 13:51–68CrossRefPubMed

16.

Abbott RA, Whittaker SJ, Morris SL et al (2009) Bexarotene therapy for mycosis fungoides and Sézary syndrome. Br J Dermatol 160:1299–1307CrossRefPubMed

17.

Lessin SR, Ross EA, Wu H (2008) Treatment of parapsoriasis with bexarotene 1% gel. Int J Dermatol 47:1325–1327CrossRefPubMed

18.

Breneman D, Sheth P, Berger V et al (2007) Phase II clinical trial of bexarotene gel 1% in psoriasis. J Drugs Dermatol 6:501–506PubMed

19.

Bedikian AY, Plager C, Papadopoulos N et al (2000) A phase II evaluation of bexarotene (Targretin) capsules in patients with metastatic melanoma. Oncol Rep 7:883–886PubMed

20.

Tsai DE, Luger SM, Andreadis C et al (2008) A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. Clin Cancer Res 14:5619–5625CrossRefPubMed

21.

Read WL, Baggstrom MQ, Fracasso PM, Govindan R (2008) A phase I study of bexarotene and rosiglitazone in patients with refractory cancers. Chemotherapy 54:236–241CrossRefPubMed

22.

Dragnev KH, Petty WJ, Shah S et al (2005) Bexarotene and erlotinib for aerodigestive tract cancer. J Clin Oncol 23:8757–8764CrossRefPubMed

23.

Hanifin JM, Stevens V, Sheth P, Breneman D (2004) Novel treatment of chronic severe hand dermatitis with bexarotene gel. Br J Dermatol 150:545–553CrossRefPubMed

24.

Talpur R, Vu J, Bassett R, Stevens V, Duvic M (2009) Phase I/II randomized bilateral half-head comparison of topical bexarotene 1% gel for alopecia areata. J Am Acad Dermatol 2009 Aug 12. [Epub ahead of print]

25.

Liu YY, Stokkel MP, Pereira AM et al (2006) Bexarotene increases uptake of radioiodide in metastases of differentiated thyroid carcinoma. Eur J Endocrinol 154:525–531CrossRefPubMed

26.

Krathen RA, Ward S, Duvic M (2003) Bexarotene is a new treatment option for lymphomatoid papulosis. Dermatology 206:142–147CrossRefPubMed

27.

Duvic M, Hymes K, Heald P et al (2001) Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II–III trial results. J Clin Oncol 19:2456–2471PubMed

28.

Duvic M, Martin AG, Kim Y et al (2001) Phase 2 and 3 clinical trial of oral bexarotene (targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol 137:581–593PubMed

29.

Kannangara AP, Levitan D, Fleischer AB Jr (2009) Evaluation of the efficacy of the combination of oral bexarotene and methotrexate for the treatment of early stage treatment-refractory cutaneous T-cell lymphoma. J Dermatolog Treat 20:169–176CrossRefPubMed

30.

Papadavid E, Antoniou C, Nikolaou V et al (2008) Safety and efficacy of low-dose bexarotene and PUVA in the treatment of patients with mycosis fungoides. Am J Clin Dermatol 9:169–173CrossRefPubMed

31.

Ramlau R, Zatloukal P, Jassem J et al (2008) Randomized phase III trial comparing bexarotene (L1069–49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. J Clin Oncol 26:1886–1892CrossRefPubMed

32.

Rigas JR, Dragnev KH (2005) Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. Oncologist 10:22–33CrossRefPubMed

33.

Rizvi N, Hawkins MJ, Eisenberg PD et al (2001) Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer 2:210–215CrossRefPubMed

34.

Esteva FJ, Glaspy J, Baidas S et al (2003) Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol 21:999–1006CrossRefPubMed

35.

D’Acunto C, Gurioli C, Neri I (2009) Plaque stage mycosis fungoides treated with bexarotene at low dosage and UVB-NB. J Dermatolog Treat 1:1–4CrossRef

36.

Foss F, Demierre MF, DiVenuti G (2005) A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 106:454–457CrossRefPubMed

37.

Yen WC, Lamph WW (2006) A selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced prostate cancer. Prostate 66:305–316CrossRefPubMed

38.

Steinhoff M, Beyer M, Roewert-Huber J et al (2008) Complete clinical remission of tumor-stage mycosis fungoides after acute extensive skin necroses, granulomatous reaction, and fever under treatment with bexarotene, vorinostat, and high-dose fenofibrate. J Am Acad Dermatol 58:S88–S91CrossRefPubMed

39.

Lokitz ML, Wong HK (2007) Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides. Photodermatol Photoimmunol Photomed 23:255–257CrossRefPubMed

40.

Altucci L, Rossin A, Hirsch O et al (2005) Rexinoid-triggered differentiation and tumor-selective apoptosis of acute myeloid leukemia by protein kinase A-mediated desubordination of retinoid X receptor. Cancer Res 65:8754–8765CrossRefPubMed

41.

Straus DJ, Duvic M, Kuzel T et al (2007) Results of a phase II trial of oral bexarotene (Targretin) combined with interferon alfa-2b (Intron-A) for patients with cutaneous T-cell lymphoma. Cancer 109:1799–1803CrossRefPubMed

42.

Feng Q, Sekula D, Guo Y et al (2008) UBE1L causes lung cancer growth suppression by targeting cyclin D1. Mol Cancer Ther 7:3780–3788CrossRefPubMed

43.

Langenfeld J, Kiyokawa H, Sekula D et al (1997) Posttranslational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism. Proc Natl Acad Sci USA 94:12070–12074CrossRefPubMed

44.

Nieto-Rementería N, Pérez-Yarza G, Boyano MD et al (2008) Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol 25:519–526

45.

Dragnev KH, Petty WJ, Shah SJ et al (2007) A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer. Clin Cancer Res 13:1794–1800CrossRefPubMed

46.

Uray IP, Shen Q, Seo HS et al (2009) Rexinoid-induced expression of IGFBP-6 requires RARbeta-dependent permissive cooperation of retinoid receptors and AP-1. J Biol Chem 284(1):345–353CrossRefPubMed

47.

Reddig PJ, Juliano RL (2005) Clinging to life: cell to matrix adhesion and cell survival. Cancer Metastasis Rev 24:425–439CrossRefPubMed

48.

Ying SX, Seal S, Abbassi N et al (2007) Differential effects of bexarotene on intrinsic and extrinsic pathways in TRAIL-induced apoptosis in two myeloid leukemia cell lines. Leuk Lymphoma 48:1003–1014CrossRefPubMed

49.

Tamm I, Wang Y, Sausville E et al (1998) IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas(CD95), Bax, Caspases, and anticancer drugs. Cancer Res 58:5315–5320PubMed

50.

Zhang C, Hazarika P, Ni X et al (2002) Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Clin Cancer Res 8:1234–1240PubMed

51.

Alyaqoub FS, Liu Y, Tao L et al (2008) Modulation by bexarotene of mRNA expression of genes in mouse lung tumors. Mol Carcinog 47:165–171CrossRefPubMed

52.

Cesario RM, Stone J, Yen WC, Bissonnette RP, Lamph WW (2006) Differentiation and growth inhibition mediated via the RXR:PPARgamma heterodimer in colon cancer. Cancer Lett 240:225–233CrossRefPubMed

53.

Kizaki M, Dawson MI, Heyman R et al (1996) Effects of novel retinoid X receptor-selective ligands on myeloid leukemia differentiation and proliferation in vitro. Blood 87:1977–1984PubMed

54.

Kuo MT (2009) Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal 11:99–133CrossRefPubMed

55.

Thiebaut F, Tsuruo T, Hamada H et al (1987) Cellular localization of the multidrug resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci 84:7735–7738CrossRefPubMed

56.

Wu K, Zhang Y, Xu XC et al (2002) The retinoid X receptor-selective retinoid, LGD1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice. Cancer Res 62:6376–6380PubMed

57.

Yen WC, Lamph WW (2005) The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma. Mol Cancer Ther 4:824–834CrossRefPubMed

58.

Yen WC, Corpuz MR, Prudente RY et al (2004) A selective retinoid X receptor agonist bexarotene (Targretin) prevents and overcomes acquired paclitaxel (Taxol) resistance in human non-small cell lung cancer. Clin Cancer Res 10:8656–8664CrossRefPubMed

59.

Yen WC, Prudente RY, Lamph WW (2004) Synergistic effect of a retinoid X receptor-selective ligand bexarotene (LGD1069, Targretin) and paclitaxel (Taxol) in mammary carcinoma. Breast Cancer Res Treat 88:141–148CrossRefPubMed

60.

Jones DR, Broad RM, Comeau LD et al (2002) Inhibition of nuclear factor kappaB chemosensitizes non-small-cell lung cancer through cytochrome c release and caspase activation. J Thorac Cardiovasc Surg 123:310–317CrossRefPubMed

61.

Bentires-Alj M, Barbu V, Fillet M et al (2003) NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells. Oncogene 22:90–97CrossRefPubMed

62.

García MG, Alaniz LD, Cordo Russo RI et al (2009) PI3K/Akt inhibition modulates multidrug resistance and activates NF-kappaB in murine lymphoma cell lines. Leuk Res 33:288–296CrossRefPubMed

63.

Nakajima Y, Madhyastha R, Maruyama M (2009) 2-Deoxy-d-ribose, a downstream mediator of thymidine phosphorylase, regulates tumor angiogenesis and progression. Anticancer Agents Med Chem 9:239–245PubMed

64.

Kumar R, Fidler IJ (1998) Angiogenic molecules and cancer metastasis. In Vivo 12:27–34PubMed

65.

Yen WC, Prudente RY, Corpuz MR et al (2006) A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer 94:654–660PubMed

Titel: Bexarotene: a promising anticancer agent
verfasst von: Liyan Qu
Xiuwen Tang
Publikationsdatum: 01.01.2010
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2010
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1140-4

Springer Medizin

Bexarotene: a promising anticancer agent

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2010

Phase I/II study of the lipiodolization using DDP-H (CDDP powder; IA-call®) in patients with unresectable hepatocellular carcinoma

Bevacizumab induced reversible thrombocytopenia in a patient with recurrent high-grade glioma: a case report

A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation

Quantitative structure–property relationships of camptothecins in humans

Phase II study of fixed dose rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie