Von Hippel-Lindau Disease: Current Challenges and Future Prospects.
VHL
Von Hippel-Lindau
hemangioblastoma
neuroendocrine tumor
pancreatic tumor
pheochromocytoma
renal cancer
second hit
tumor formation
tumor suppressor gene
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
02
2020
accepted:
20
05
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
2
7
2020
Statut:
epublish
Résumé
Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs. A consequent screening and timely preventive treatment of lesions are crucial for patients affected by VHL disease. Surgical indications and treatment have been evaluated and optimized over many years. In the last decade, pharmacological therapies have been evolving, but are largely still at an experimental stage. Effective pharmacological therapy as well as detection of biomarkers is based on the understanding of the molecular basis of disease. The molecular basis of von Hippel-Lindau disease is the loss of function of the VHL protein and subsequent accumulation of hypoxia-inducible factor with downstream effects on cellular metabolism and differentiation. Organs affected by VHL disease may develop frank tumors. More characteristically, however, they reveal multiple separate microscopic foci of neoplastic cell proliferation. The exact mechanisms of tumorigenesis in VHL disease are, however, still not entirely understood and knowledge on biomarkers and targeted therapy is scarce.
Identifiants
pubmed: 32606780
doi: 10.2147/OTT.S190753
pii: 190753
pmc: PMC7305855
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
5669-5690Informations de copyright
© 2020 Gläsker et al.
Déclaration de conflit d'intérêts
Prof. Dr. Christian A Koch received royalties for book and editorship from Springer and Elsevier. He also received honorarium as a consultant for DOC events. The authors report no other conflicts of interest in this work.
Références
Nat Rev Cancer. 2003 Oct;3(10):721-32
pubmed: 13130303
N Engl J Med. 2006 Oct 5;355(14):1419-31
pubmed: 17021318
Eur Urol Focus. 2016 Feb;1(3):231-240
pubmed: 28078330
Acta Ophthalmol. 2010 Jun;88(4):e137-8
pubmed: 19681788
Pediatr Blood Cancer. 2009 Sep;53(3):464-7
pubmed: 19415739
Fam Cancer. 2012 Sep;11(3):387-94
pubmed: 22426863
Nature. 1999 May 20;399(6733):271-5
pubmed: 10353251
Ophthalmol Retina. 2017 May-Jun;1(3):181-187
pubmed: 28670632
N Engl J Med. 1999 Jun 17;340(24):1872-9
pubmed: 10369850
Clin Cancer Res. 1999 Nov;5(11):3669-75
pubmed: 10589785
Head Neck. 2012 May;34(5):632-7
pubmed: 21692132
Endocr Relat Cancer. 2013 Dec 16;21(1):17-25
pubmed: 24169644
Acta Ophthalmol. 2012 Mar;90(2):e157-8
pubmed: 21649868
Graefes Arch Clin Exp Ophthalmol. 1999 Jun;237(6):513-7
pubmed: 10379614
AJR Am J Roentgenol. 1992 Dec;159(6):1229-34
pubmed: 1442389
Cancer Res. 1995 Mar 15;55(6):1358-64
pubmed: 7533661
J Clin Neurosci. 2018 Apr;50:154-156
pubmed: 29396065
Oncogene. 2000 Nov 16;19(48):5435-43
pubmed: 11114720
Clin Oncol (R Coll Radiol). 2004 Dec;16(8):585-6
pubmed: 15630860
Fam Cancer. 2015 Jun;14(2):309-16
pubmed: 25391617
Surgery. 1998 Dec;124(6):1153-9
pubmed: 9854597
Urol Int. 2012;88(1):71-8
pubmed: 22156657
Lancet. 2003 Jun 14;361(9374):2059-67
pubmed: 12814730
J Neurosurg. 2003 Jan;98(1):82-94
pubmed: 12546356
J Pathol. 2008 Dec;216(4):514-20
pubmed: 18836991
Ann Oncol. 2011 Dec;22(12):2661-6
pubmed: 22105611
J Clin Gastroenterol. 2015 Jan;49(1):89-90
pubmed: 24921213
Target Oncol. 2012 Jun;7(2):145-9
pubmed: 22374327
J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62
pubmed: 10567493
Hum Mutat. 1996;8(4):348-57
pubmed: 8956040
J Natl Cancer Inst. 2012 May 2;104(9):700-8
pubmed: 22517990
Trans Am Ophthalmol Soc. 2005;103:495-511
pubmed: 17057815
Klin Monbl Augenheilkd. 2008 Apr;225(4):292-4
pubmed: 18401796
World J Surg. 2020 Feb;44(2):570-577
pubmed: 31773218
Science. 1993 May 28;260(5112):1317-20
pubmed: 8493574
Cancer Res. 1998 Feb 1;58(3):504-8
pubmed: 9458097
Clin Endocrinol (Oxf). 2008 Aug;69(2):181-8
pubmed: 18394016
J Clin Endocrinol Metab. 2011 Mar;96(3):717-25
pubmed: 21190975
Gastroenterology. 1991 Aug;101(2):465-71
pubmed: 2065922
Urology. 1997 Jun;49(6):926-31
pubmed: 9187702
Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3788-93
pubmed: 14506172
N Engl J Med. 2002 May 9;346(19):1459-66
pubmed: 12000816
Cancer Cell. 2002 Jun;1(5):459-68
pubmed: 12124175
J Clin Oncol. 2005 May 20;23(15):3624-6
pubmed: 15908674
J Clin Endocrinol Metab. 2009 Dec;94(12):4757-67
pubmed: 19864450
Am J Pathol. 1998 Jul;153(1):223-31
pubmed: 9665483
Eur J Endocrinol. 2009 Sep;161(3):495-502
pubmed: 19574279
J Med Genet. 1991 Jul;28(7):443-7
pubmed: 1895313
Surv Ophthalmol. 2001 Sep-Oct;46(2):117-42
pubmed: 11578646
Curr Opin Cell Biol. 2001 Apr;13(2):167-71
pubmed: 11248550
J Clin Endocrinol Metab. 2009 Feb;94(2):386-91
pubmed: 19017755
J Pathol. 2006 Sep;210(1):32-41
pubmed: 16841375
Q J Med. 1990 Nov;77(283):1151-63
pubmed: 2274658
J Chin Med Assoc. 2014 Jan;77(1):52-6
pubmed: 24206762
J Am Coll Surg. 2011 Apr;212(4):659-65; discussion 665-7
pubmed: 21463807
Intern Med. 2016;55(6):629-34
pubmed: 26984080
Oncogene. 2018 Jan 11;37(2):139-147
pubmed: 28925400
Can Urol Assoc J. 2015 Sep-Oct;9(9-10):E651-3
pubmed: 26425233
Endocr Relat Cancer. 2011 Dec 01;18(6):R253-76
pubmed: 22041710
Mol Cell Biol. 1998 Feb;18(2):732-41
pubmed: 9447969
J Med Genet. 2012 Apr;49(4):264-9
pubmed: 22362873
Eur J Med Res. 2000 Feb 28;5(2):47-58
pubmed: 10720563
J Pathol. 2006 Nov;210(3):374-82
pubmed: 16981244
Blood. 1990 Feb 1;75(3):577-82
pubmed: 2297568
Hum Mutat. 2010 May;31(5):521-37
pubmed: 20151405
J Neurosurg. 2018 Oct 1;:1-9
pubmed: 30497198
Hered Cancer Clin Pract. 2019 Jul 29;17:22
pubmed: 31384339
Sci Rep. 2017 Jan 17;7:40822
pubmed: 28094316
Trans Am Clin Climatol Assoc. 2017;128:298-307
pubmed: 28790514
Endocr Relat Cancer. 2018 Sep;25(9):783-793
pubmed: 29748190
Sci Rep. 2019 Jul 11;9(1):10062
pubmed: 31296894
Hered Cancer Clin Pract. 2018 Jan 5;16:2
pubmed: 29312473
J Clin Oncol. 2012 May 1;30(13):e137-9
pubmed: 22393103
Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6290S-5S
pubmed: 15448019
Int J Surg Pathol. 2000 Jul;8(3):207-212
pubmed: 11493991
Ophthalmology. 2011 Jan;118(1):142-9
pubmed: 20801520
Pancreas. 2017 Aug;46(7):948-952
pubmed: 28697137
J Cancer Res Ther. 2015 Oct-Dec;11(4):920-2
pubmed: 26881543
Neoplasia. 2008 Oct;10(10):1146-53
pubmed: 18813354
PLoS Med. 2007 Feb;4(2):e60
pubmed: 17298169
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10595-9
pubmed: 8855223
Expert Rev Anticancer Ther. 2007 Dec;7(12):1737-47
pubmed: 18062748
J Clin Endocrinol Metab. 2015 Dec;100(12):4498-504
pubmed: 26451910
Ann Surg. 2015 Aug;262(2):384-8
pubmed: 25185468
Open Ophthalmol J. 2010 Oct 21;4:66-9
pubmed: 21293730
Lancet Oncol. 2018 Oct;19(10):1351-1359
pubmed: 30236511
Urology. 2018 Sep;119:140-142
pubmed: 29545044
Arch Pathol Lab Med. 2010 Apr;134(4):630-3
pubmed: 20367315
J Clin Endocrinol Metab. 1999 Aug;84(8):2608-10
pubmed: 10443647
Eur J Nucl Med. 1995 Apr;22(4):382-4
pubmed: 7607270
Genes Dev. 1998 Jan 15;12(2):149-62
pubmed: 9436976
Urol Oncol. 2004 May-Jun;22(3):193-6
pubmed: 15271314
Eur J Nucl Med Mol Imaging. 2016 Oct;43(11):2014-20
pubmed: 27293206
Contrib Nephrol. 2001;(136):193-207
pubmed: 11688380
Am J Case Rep. 2017 Nov 17;18:1220-1224
pubmed: 29146893
JAMA. 2007 Jul 4;298(1):41-8
pubmed: 17609489
Neuropathol Appl Neurobiol. 2005 Dec;31(6):618-22
pubmed: 16281910
J Neuropathol Exp Neurol. 1996 May;55(5):522-7
pubmed: 8627342
AJR Am J Roentgenol. 1994 May;162(5):1091-4
pubmed: 8165988
Invest Ophthalmol Vis Sci. 2000 Jun;41(7):1909-15
pubmed: 10845616
Exp Mol Pathol. 2017 Apr;102(2):255-261
pubmed: 28214514
Medicine (Baltimore). 1989 Jan;68(1):1-29
pubmed: 2642584
J Neurosurg. 2003 Jan;98(1):95-105
pubmed: 12546357
Am J Pathol. 1997 Oct;151(4):951-6
pubmed: 9327728
Cancer. 1999 Dec 1;86(11 Suppl):2478-82
pubmed: 10630173
J Urol. 2003 Dec;170(6 Pt 1):2163-72
pubmed: 14634372
Can J Ophthalmol. 2009 Oct;44(5):608-9
pubmed: 19789606
J Oncol Pharm Pract. 2019 Dec;25(8):2049-2051
pubmed: 31694494
Ophthalmology. 2002 Oct;109(10):1799-806
pubmed: 12359597
Eur J Endocrinol. 2012 Feb;166(2):151-8
pubmed: 21896620
Neuro Oncol. 2010 Jan;12(1):80-6
pubmed: 20150370
Orphanet J Rare Dis. 2015 Sep 22;10:118
pubmed: 26394686
J Am Coll Surg. 2014 Feb;218(2):163-9
pubmed: 24440063
World Neurosurg. 2014 Sep-Oct;82(3-4):e495-501
pubmed: 23396070
Blood. 2002 May 15;99(10):3851-3
pubmed: 11986247
Hum Pathol. 1978 Mar;9(2):181-8
pubmed: 640643
Oncotarget. 2018 May 4;9(34):23390-23395
pubmed: 29805741
Neuro Endocrinol Lett. 2015 Dec;36(6):517-20
pubmed: 26812297
J Gastrointest Oncol. 2019 Aug;10(4):645-651
pubmed: 31392045
Lancet. 1991 Jul 27;338(8761):258
pubmed: 1676812
Oncotarget. 2018 Apr 13;9(28):20058-20074
pubmed: 29732003
Hum Pathol. 1997 May;28(5):540-3
pubmed: 9158701
Endocr Pathol. 2002 Spring;13(1):17-27
pubmed: 12114747
Hered Cancer Clin Pract. 2018 Sep 11;16:15
pubmed: 30214643
Ann Surg. 2019 Apr;269(4):741-747
pubmed: 29334561
Am J Pathol. 2000 Nov;157(5):1615-21
pubmed: 11073821
Ann Surg. 2002 May;235(5):713-20; discussion 720-1
pubmed: 11981218
J Clin Endocrinol Metab. 2009 Nov;94(11):4367-71
pubmed: 19808854
J Endocr Soc. 2019 Jul 02;3(9):1682-1692
pubmed: 31528828
Adv Nephrol Necker Hosp. 1994;23:1-27
pubmed: 8154348
Eur J Endocrinol. 2017 May;176(5):575-582
pubmed: 28289088
Oncotarget. 2017 Feb 21;8(8):13979-13985
pubmed: 28103578
Retina. 2007 Feb;27(2):150-8
pubmed: 17290195
Surgery. 2000 Dec;128(6):1022-7;discussion 1027-8
pubmed: 11114638
Neurosurgery. 2003 Dec;53(6):1306-13; discussion 1313-4
pubmed: 14633297
Cancers (Basel). 2019 Oct 08;11(10):
pubmed: 31597347
Cancer. 1989 Dec 1;64(11):2292-302
pubmed: 2804921
Neurosurgery. 2010 Sep;67(3 Suppl Operative):ons300-3; discussion ons303
pubmed: 20679920
World J Surg. 2011 Mar;35(3):563-7
pubmed: 21181474
Ann Neurol. 2004 May;55(5):721-8
pubmed: 15122713
N Engl J Med. 2019 Aug 8;381(6):552-565
pubmed: 31390501
CNS Oncol. 2015;4(6):387-92
pubmed: 26497655
J Urol. 1995 Dec;154(6):2010-4; discussion 2014-5
pubmed: 7500446
Acta Ophthalmol. 2010 Nov;88(7):e271-2
pubmed: 20977691
Ophthalmology. 2002 Sep;109(9):1745-51
pubmed: 12208726
Orphanet J Rare Dis. 2017 Jun 29;12(1):122
pubmed: 28662711
J Neurooncol. 2011 Jan;101(2):307-10
pubmed: 20524042
Nat Clin Pract Urol. 2005 May;2(5):248-55
pubmed: 16474836
Am J Ophthalmol. 2003 Jul;136(1):194-6
pubmed: 12834696
Curr Mol Med. 2004 Dec;4(8):833-42
pubmed: 15579030
Scand J Gastroenterol. 2015 Mar;50(3):360-7
pubmed: 25562111
Curr Opin Cell Biol. 2007 Dec;19(6):685-90
pubmed: 18006292
J Neurosurg. 1960 Jul;17:751-61
pubmed: 13834086
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2156-61
pubmed: 9122164
J Int Med Res. 2019 Feb;47(2):973-981
pubmed: 30178691
Nat Med. 1995 Aug;1(8):822-6
pubmed: 7585187
Cancer Imaging. 2016 Aug 17;16(1):22
pubmed: 27535829
J Urol. 1999 Sep;162(3 Pt 1):659-64
pubmed: 10458336
JAMA. 2004 Feb 25;291(8):943-4
pubmed: 14982909
Cancer Biol Ther. 2018;19(9):766-772
pubmed: 29947576
JAMA Netw Open. 2019 Aug 2;2(8):e198898
pubmed: 31397861
J Neurosurg. 2014 May;120(5):1055-62
pubmed: 24579662
Clin Chem. 2011 Mar;57(3):411-20
pubmed: 21262951
Genes Dev. 1999 Jul 15;13(14):1822-33
pubmed: 10421634
Nat Cell Biol. 2008 Mar;10(3):361-9
pubmed: 18297059
Am J Pathol. 1996 Dec;149(6):2089-94
pubmed: 8952541
Cancer Res. 2005 Dec 1;65(23):10847-53
pubmed: 16322231
Br J Neurosurg. 2013 Dec;27(6):847-9
pubmed: 23705578
Brain. 2007 Mar;130(Pt 3):836-42
pubmed: 17264095
Cancer Res. 2003 Nov 1;63(21):7051-5
pubmed: 14612494
Nat Rev Endocrinol. 2011 Sep 06;7(12):749-55
pubmed: 21894215
Surgery. 2011 Dec;150(6):1194-201
pubmed: 22136840
Nat Clin Pract Endocrinol Metab. 2009 Feb;5(2):76-7
pubmed: 19165218
Clin Genitourin Cancer. 2018 Aug;16(4):266-273
pubmed: 29503246
J Clin Invest. 2015 May;125(5):1987-97
pubmed: 25866969
JAMA. 1997 May 14;277(18):1461-6
pubmed: 9145719
Medicine (Baltimore). 1997 Nov;76(6):381-91
pubmed: 9413424
Neurosurgery. 2013 Jun;72(6):930-5; discussion 935
pubmed: 23407287
J Clin Endocrinol Metab. 2009 Jun;94(6):1938-44
pubmed: 19336503
J Urol. 1999 May;161(5):1475-9
pubmed: 10210376
Mod Pathol. 2011 Aug;24(8):1023-30
pubmed: 21499240
Clin Genitourin Cancer. 2017 Aug 10;:
pubmed: 28866246
Cancer Res. 2006 Apr 15;66(8):4167-72
pubmed: 16618738
J Urol. 1995 Jan;153(1):22-6
pubmed: 7966777
Cancer Res Treat. 2013 Dec;45(4):349-53
pubmed: 24454008
Hum Pathol. 1988 Sep;19(9):1072-9
pubmed: 3417291
Pancreas. 2017 Aug;46(7):e57
pubmed: 28697140
Exp Mol Pathol. 2014 Apr;96(2):162-7
pubmed: 24394472
World J Surg. 2002 Aug;26(8):1005-12
pubmed: 12045858
J Clin Endocrinol Metab. 2002 May;87(5):1955-60
pubmed: 11994324
Pancreas. 2012 Apr;41(3):492-3
pubmed: 22415670
Ophthalmology. 2008 Nov;115(11):1957-64
pubmed: 18789534
Cancer Res. 1993 Oct 15;53(20):4745-9
pubmed: 8402652
Arch Ophthalmol. 1999 May;117(5):625-30
pubmed: 10326959
Nat Rev Cancer. 2002 Sep;2(9):673-82
pubmed: 12209156
J Urol. 1995 Mar;153(3 Pt 2):913-6
pubmed: 7853573
J Clin Neurosci. 2013 Sep;20(9):1269-75
pubmed: 23845264
Oncotarget. 2016 Dec 20;7(51):85306-85317
pubmed: 27852035
Ann Neurol. 2005 Sep;58(3):392-9
pubmed: 16130092
Am J Clin Pathol. 1978 Mar;69(3):289-98
pubmed: 637043