Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2010

01-01-2010 | Mini Review

Bexarotene: a promising anticancer agent

Authors: Liyan Qu, Xiuwen Tang

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2010

Login to get access

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.
Literature
1.
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
2.
Lotan R (1996) Retinoids in cancer prevention. FASEB 10:1031–1039
3.
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
4.
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
5.
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
6.
Dragnev KH, Rigas JR, Dmitrovsky E (2000) The retinoids and cancer prevention mechanisms. Oncologist 5:361–368CrossRefPubMed
7.
Niles RM (2000) Recent advances in the use of vitamin A (retinoids) in the prevention and treatment of cancer. Nutrition 16:1084–1089CrossRefPubMed
8.
Toma S, Raffo P, Isnardi L et al (1999) Retinoids in lung cancer chemoprevention and treatment. Ann Oncol 10:95–102CrossRef
9.
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
Metadata
Title
Bexarotene: a promising anticancer agent
Authors
Liyan Qu
Xiuwen Tang
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-009-1140-4

Other articles of this Issue 2/2010

Cancer Chemotherapy and Pharmacology 2/2010 Go to the issue

Original Article

Phase 1 first-in-human clinical study of S-trans, trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors

Original Article

The effect of transcatheter arterial chemoembolization on phase II drug metabolism enzymes in patients with hepatocellular carcinoma

Clinical Trial Report

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

Short Communication

The contribution of deleterious DPYD gene sequence variants to fluoropyrimidine toxicity in British cancer patients

Clinical Trial Report

A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma

Original Article

Preclinical rationale for combined use of endocrine therapy and 5-fluorouracil but neither doxorubicin nor paclitaxel in the treatment of endocrine-responsive breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits