Molecular pathways: Current role and future directions of the retinoic acid pathway in cancer prevention and treatment

Clinical Cancer Research

Volumn 19, Issue 7, 2013, Pages 1651-1959

  Connolly, Roisin M ^a   Nguyen, Nguyen K ^a   Sukumar, Saraswati ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALITRETINOIN; BETA CAROTENE; BEXAROTENE; CISPLATIN; FENRETINIDE; ISOTRETINOIN; NAVELBINE; PACLITAXEL; PLACEBO; PMID 11352969; RETINOIC ACID; RETINOIC ACID RECEPTOR; RETINOIC ACID RECEPTOR BETA; TAMOXIFEN; UNCLASSIFIED DRUG;

ADVANCED CANCER; BREAST CANCER; CANCER PREVENTION; CANCER STEM CELL; CANCER SURVIVAL; DISEASE FREE SURVIVAL; DOSE RESPONSE; DRUG APPROVAL; DRUG EFFECT; DRUG MECHANISM; DRUG MEGADOSE; EPIGENETICS; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE LOCATION; HEAD AND NECK CANCER; HUMAN; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; METASTASIS; NONHUMAN; ONCOGENE; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RETINOID ACID RECEPTOR BETA GENE; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; TREATMENT DURATION;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; RECEPTORS, RETINOIC ACID; RETINOIDS; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH; TRETINOIN;

EID: 84877091761     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-3175     Document Type: Review

References (80)

1. Theodosiou M, Laudet V, Schubert M. From carrot to clinic: an overview of the retinoic acid signaling pathway. Cell Mol Life Sci 2010;67:1423-45.
2. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs 1997;53:358-88. (Pubitemid 27117359)
3. Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase IIIII trial results. J Clin Oncol 2001;19:2456-71. (Pubitemid 32391217)
4. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997;337:1021-8. (Pubitemid 27430519)
5. Bushue N, Wan YJ. Retinoid pathway and cancer therapeutics. Adv Drug Deliv Rev 2010;62:1285-98.
6. Alvarez S, Germain P, Alvarez R, Rodriguez-Barrios F, Gronemeyer H, de Lera AR. Structure, function and modulation of retinoic acid receptor beta, a tumor suppressor. Int J Biochem Cell Biol 2007;39:1406-15. (Pubitemid 47031031)
7. Ross-Innes CS, Stark R, Holmes KA, Schmidt D, Spyrou C, Russell R, et al. Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev 2010;24:171-82.
8. Tang XH, Gudas LJ. Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 2011;6:345-64.
9. Cras A, Politis B, Balitrand N, Darsin-Bettinger D, Boelle PY, Cassinat B, et al. Bexarotene via CBP/p300 induces suppression of NF-kappaB-dependent cell growth and invasion in thyroid cancer. Clin Cancer Res 2012;18:442-53.
10. Papi A, Guarnieri T, Storci G, Santini D, Ceccarelli C, Taffurelli M, et al. Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells. Cell Death Differ 2012;19:1208-19.
11. Ying M, Wang S, Sang Y, Sun P, Lal B, Goodwin CR, et al. Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition. Oncogene 2011;30:3454-67.
12. Lu TY, Li WC, Chen RY, Fan QX, Wang LX, Wang RL, et al. Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice. Chinese Med J 2011;124:2708-14.
13. Piskunov A, Rochette-Egly C. A retinoic acid receptor RARalpha pool present in membrane lipid rafts forms complexes with G protein alphaQ to activate p38MAPK. Oncogene 2012;31:3333-45.
14. Dilworth FJ, Chambon P. Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene 2001;20:3047-54. (Pubitemid 32553559)
15. Hua S, Kittler R, White KP. Genomic antagonism between retinoic acid and estrogen signaling in breast cancer. Cell 2009;137:1259-71.
16. Lefebvre P, Martin PJ, Flajollet S, Dedieu S, Billaut X, Lefebvre B. Transcriptional activities of retinoic acid receptors. Vitam Horm 2005;70:199-264. (Pubitemid 43589019)
17. Schug TT, Berry DC, Shaw NS, Travis SN, Noy N. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell 2007;129:723-33. (Pubitemid 46802374)
18. Wan YJ, An D, Cai Y, Repa JJ, Hung-Po Chen T, Flores M, et al. Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver. Mol Cell Biol 2000;20:4436-44. (Pubitemid 30346638)
19. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 1995;9:1033-45.
20. Wang Q, Lee D, Sysounthone V, Chandraratna RAS, Christakos S, Korah R, et al. 1,25-dihydroxyvitamin D3 and retinoic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat 2001;67:157-68. (Pubitemid 32744496)
21. Houle B, Rochette-Egly C, Bradley WE. Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells. Proc Natl Acad Sci U S A 1993;90:985-9. (Pubitemid 23053935)
22. Freemantle SJ, Spinella MJ, Dmitrovsky E. Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene 2003;22:7305-15. (Pubitemid 37487162)
23. Liu Y, Lee MO, Wang HG, Li Y, Hashimoto Y, Klaus M, et al. Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol Cell Biol 1996;16:1138-49. (Pubitemid 26061685)
24. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996;10:940-54. (Pubitemid 26285969)
25. Sirchia SM, Ferguson AT, Sironi E, Subramanyan S, Orlandi R, Sukumar S, et al. Evidence of epigenetic changes affecting the chromatin state of the retinoic acid receptor beta2 promoter in breast cancer cells. Oncogene 2000;19:1556-63. (Pubitemid 30175677)
26. Catalano A,Dawson MA,Somana K, Opat S, Schwarer A, Campbell LJ, et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood 2007;110:4073-6. (Pubitemid 350248464)
27. Pandolfi PP. Oncogenes and tumor suppressors in the molecular pathogenesis of acute promyelocytic leukemia. Hum Mol Genet 2001;10:769-75. (Pubitemid 32331587)
28. Lotan R, Xu XC, Lippman SM, Ro JY, Lee JS, Lee JJ, et al. Suppression of retinoic acid receptor-beta in premalignant oral lesions and its upregulation by isotretinoin. N Engl Med 1995;332:1405-10.
29. Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, et al. 13-cisretinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986;315:1501-5. (Pubitemid 17052146)
30. Lippman SM, Batsakis JG, Toth BB, Weber RS, Lee JJ, Martin JW, et al. Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med 1993;328:15-20. (Pubitemid 23011466)
31. Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Interventions for treating oral leukoplakia. Cochrane Database Syst Rev 2006;CD001829.
32. Khuri FR, Lee JJ, Lippman SM, Kim ES, Cooper JS, Benner SE, et al. Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients. J Natl Cancer Inst 2006;98:441-50.
33. Lee HY, Sueoka N, Hong WK, Mangelsdorf DJ, Claret FX, Kurie JM. Alltrans-retinoic acid inhibits Jun N-terminal kinase by increasing dualspecificity phosphatase activity. Mol Cell Biol 1999;19:1973-80. (Pubitemid 29098255)
34. Sun SY, Yue P, Chandraratna RA, Tesfaigzi Y, Hong WK, Lotan R. Dual mechanisms of action of the retinoid CD437: nuclear retinoic acid receptor-mediated suppression of squamous differentiation and receptor-independent induction of apoptosis in UMSCC22B human head and neck squamous cell carcinoma cells. Mol Pharmacol 2000;58:508-14.
35. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994;330:1029-35.
36. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5. (Pubitemid 26137973)
37. Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. Betacarotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst 1999;91:2102-6. (Pubitemid 30019571)
38. Virtamo J, Pietinen P, Huttunen JK, Korhonen P, Malila N, Virtanen MJ, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003;290:476-85. (Pubitemid 37430501)
39. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, et al. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 2004;96:1743-50. (Pubitemid 39654568)
40. Lee JS, Lippman SM, Benner SE, Lee JJ, Ro JY, Lukeman JM, et al. Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia. J Clin Oncol 1994;12:937-45. (Pubitemid 24145320)
41. Kurie JM, Lee JS, Khuri FR, Mao L, Morice RC, Lee JJ, et al. N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and dysplasia of the bronchial epithelium. Clin Cancer Res 2000;6:2973-9. (Pubitemid 30637717)
42. Kelly K, Kittelson J, Franklin WA, Kennedy TC, Klein CE, Keith RL, et al. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer. Cancer Prev Res (Phila) 2009;2:440-9.
43. Lippman SM, Lee JJ, Karp DD, Vokes EE, Benner SE, Goodman GE, et al. Randomized phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 2001;93:605-18.
44. van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000;92:977-86.
45. Pastorino U, Infante M, Maioli M, Chiesa G, Buyse M, Firket P, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993;11:1216-22. (Pubitemid 23199122)
46. Kurie JM, Lotan R, Lee JJ, Lee JS, Morice RC, Liu DD, et al. Treatment of former smokers with 9-cis-retinoic acid reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl Cancer Inst 2003;95:206-14. (Pubitemid 36240633)
47. Pappas JJ, Toulouse A, Basik M, Levesque L, Bradley WE. Knockdown of RARB2 identifies a dual role in cancer. Genes Chromosomes Cancer 2011;50:700-14.
48. Lin LM, Li BX, Xiao JB, Lin DH, Yang BF. Synergistic effect of all-transretinoic acid and arsenic trioxide on growth inhibition and apoptosis in human hepatoma, breast cancer, and lung cancer cells in vitro. World J Gastroenterol 2005;11:5633-7.
49. Kucukzeybek Y, Gul MK, Cengiz E, Erten C, Karaca B, Gorumlu G, et al. Enhancement of docetaxel-induced cytotoxicity and apoptosis by alltrans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145. J Exp Clin Cancer Res 2008;27:37.
50. Arrieta O, Gonzalez-De la Rosa CH, Arechaga-Ocampo E, Villanueva-Rodriguez G, Ceron-Lizarraga TL, Martinez-Barrera L, et al. Randomized phase II trial of All-trans-retinoic acidwith chemotherapy based on paclitaxel and cisplatin as first-line treatment in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010;28:3463-71.
51. Khuri FR, Rigas JR, Figlin RA, Gralla RJ, Shin DM, Munden R, et al. Multi-institutional phase I/II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer. J Clin Oncol 2001;19:2626-37. (Pubitemid 32441367)
52. Ramlau R, Zatloukal P, Jassem J, Schwarzenberger P, Orlov SV, Gottfried M, et al. 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 2008;26:1886-92.
53. Moon RC, Thompson HJ, Becci PJ, Grubbs CJ, Gander RJ, Newton DL, et al. N-(4-Hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res 1979;39:1339-46. (Pubitemid 9183854)
54. Mehta RG,Moon RC, Hawthorne M, Formelli F, Costa A. Distribution of fenretinide in the mammary gland of breast cancer patients. Eur J Cancer 1991;27:138-41.
55. Veronesi U, De Palo G, Marubini E, Costa A, Formelli F, Mariani L, et al. Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst 1999;91:1847-56.
56. Bonanni B, Lazzeroni M. Retinoids and breast cancer prevention. Recent Results Cancer Res 2009;181:77-82.
57. Ratko TA, Detrisac CJ, Dinger NM, Thomas CF, Kelloff GJ, Moon RC. Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats. Cancer Res 1989;49:4472-6. (Pubitemid 19208347)
58. 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.
59. Cassidy J, Lippman M, Lacroix A, Peck G. Phase II trial of 13-cis-retinoic acid in metastatic breast cancer. Eur J Cancer Clin Oncol 1982;18:925-8. (Pubitemid 13147891)
60. Sutton LM, Warmuth MA, Petros WP, Winer EP. Pharmacokinetics and clinical impact of all-trans retinoic acid in metastatic breast cancer: a phase II trial. Cancer Chemother Pharmacol 1997;40:335-41. (Pubitemid 27276138)
61. Esteva FJ, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, et al. Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol 2003;21:999-1006. (Pubitemid 46594127)
62. Chiesa MD, Passalacqua R, Michiara M, Franciosi V, Di Costanzo F, Bisagni G, et al. Tamoxifen vs tamoxifen plus 13-cis-retinoic acid vs tamoxifen plus interferon alpha-2a as first-line endocrine treatments in advanced breast cancer: updated results of a phase II, prospective, randomised multicentre trial. Acta Bio-Medica 2007;78:204-9. (Pubitemid 351599000)
63. Bryan M, Pulte ED, Toomey KC, Pliner L, Pavlick AC, Saunders T, et al. A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer. Invest N Drugs 2011;29:1482-7.
64. Fenaux P, Wang ZZ, Degos L. Treatment of acute promyelocytic leukemia by retinoids. Curr Pics Microbiol and Immunol 2007;313:101-28. (Pubitemid 47400335)
65. Widschwendter M, Berger J, Daxenbichler G, Muller-Holzner E, Widschwendter A, Mayr A, et al. Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer. Cancer Res 1997;57:4158-61. (Pubitemid 27413413)
66. Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J, et al. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res 2004;10:3104-9. (Pubitemid 38619690)
67. Sirchia SM, Ren M, Pili R, Sironi E, Somenzi G, Ghidoni R, et al. Endogenous reactivation of the RARbeta2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Res 2002;62:2455-61. (Pubitemid 34462717)
68. Qian DZ, Ren M, Wei Y, Wang X, van de Geijn F, Rasmussen C, et al. In vivo imaging of retinoic acid receptor beta2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cells. The Prostate 2005;64:20-8. (Pubitemid 40734735)
69. Pili R, Salumbides B, Zhao M, Altiok S, Qian D, Zwiebel J, et al. Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours. Br J Cancer 2012;106:77-84.
70. Raffoux E, Cras A, Recher C, Boelle PY, de Labarthe A, Turlure P, et al. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Oncotarget 2010;1:34-42.
71. Nguyen N, Korangath P, Sabnis G, Brodie A, Ordentlich P, Stearns V, et al. A combination of HDAC inhibitor entinostat (MS-275), all trans retinoic acid (ATRA) and low dose doxorubicin causes regression of established xenografts of triple negative breast cancer [abstract]. In: Proceedings of the 101st Annual Meeting at American Association for Cancer Research; 2010 Apr 17-21, Washington, DC. Philadelphia (PA): AACR; 2010. Abstract nr 5593.
72. Lee ER, Murdoch FE, Fritsch MK. High histone acetylation and decreased polycomb repressive complex 2 member levels regulate gene specific transcriptional changes during early embryonic stem cell differentiation induced by retinoic acid. Stem Cells 2007;25:2191-9. (Pubitemid 47480477)
73. Gillespie RF, Gudas LJ. Retinoid regulated association of transcriptional co-regulators and the polycomb group protein SUZ12 with the retinoic acid response elements of Hoxa1, RARbeta(2), and Cyp26A1 in F9 embryonal carcinoma cells. J Mol Biol 2007;372:298-316. (Pubitemid 47267961)
74. Moghal N, Neel BG. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer. Mol Cell Biol 1995;15:3945-59.
75. White JA, Beckett-Jones B, Guo YD, Dilworth FJ, Bonasoro J, Jones G, et al. cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem 1997;272:18538-41. (Pubitemid 27318190)
76. McPherson LA, Woodfield GW, Weigel RJ. AP2 transcription factors regulate expression of CRABPII in hormone responsive breast carcinoma. J Surg Res 2007;138:71-8. (Pubitemid 46227455)
77. Ren M, Pozzi S, Bistulfi G, Somenzi G, Rossetti S, Sacchi N. Impaired retinoic acid (RA) signal leads to RARbeta2 epigenetic silencing andRA resistance. Mol Cell Biol 2005;25:10591-603. (Pubitemid 41681979)
78. Lippman SM, Shin DM, Lee JJ, Batsakis JG, Lotan R, Tainsky MA, et al. p53 and retinoid chemoprevention of oral carcinogenesis. Cancer Res 1995;55:16-9.
79. Duong V, Rochette-Egly C. The molecular physiology of nuclear retinoic acid receptors. From health to disease. Biochim Biophys Acta 2011;18:1023-31.
80. Njar VC, Gediya L, Purushottamachar P, Chopra P, Vasaitis TS, Khandelwal A, et al. Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases. Bioorganic Med Chem 2006;14:4323-40. (Pubitemid 43728662)