Home LiteratureArticle Details
PMID: 27325049 Published · ppublish English Journal Article Review Research Support, N.I.H., Intramural

Therapeutic Strategies for Hereditary Kidney Cancer.

Current oncology reports ·Vol. 18 ·No. 8 ·2016-00-00 ·Pages 50

Sidana A, Srinivasan R

Abstract

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

Keywords
Clear cell renal cell cancer Fumarate hydratase HLRCC HPRC Hereditary Inherited Kidney cancer Metastatic Papillary renal cell cancer Renal cell cancer Succinate dehydrogenase Tuberous sclerosis Tyrosine kinase inhibitors Von Hippel-Lindau
MeSH Terms
Antineoplastic Agents/therapeutic use Carcinoma, Renal Cell/genetics,therapy Clinical Trials as Topic Genetic Predisposition to Disease/genetics Humans Kidney Neoplasms/genetics,therapy Models, Genetic Mutation Nephrectomy/methods Signal Transduction/genetics
Chemicals
Antineoplastic Agents
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sidana Abhinav
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 - Hatfield CRC, Room 1-5940, Bethesda, MD, 20892, USA. abhinav.sidana@nih.gov.
Srinivasan Ramaprasad
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 - Hatfield CRC, Room 1-5940, Bethesda, MD, 20892, USA.
References (53)
53 references, click to expand
  1. Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer.
    J Urol. 2012 Dec;188(6):2063-71 PMID: 23083876
  2. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.
    Nature. 1999 May 20;399(6733):271-5 PMID: 10353251
  3. Evaluation and management of renal tumors in the Birt-Hogg-Dubé syndrome.
    J Urol. 2005 May;173(5):1482-6 PMID: 15821464
  4. Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.
    Clin Endocrinol (Oxf). 2008 Oct;69(4):587-96 PMID: 18419787
  5. Germline SDHB mutations and familial renal cell carcinoma.
    J Natl Cancer Inst. 2008 Sep 3;100(17):1260-2 PMID: 18728283
  6. Aerobic glycolysis: a novel target in kidney cancer.
    Expert Rev Anticancer Ther. 2013 Jun;13(6):711-9 PMID: 23773105
  7. Papillary renal cell carcinoma: A review of the current therapeutic landscape.
    Crit Rev Oncol Hematol. 2015 Oct;96(1):100-12 PMID: 26052049
  8. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.
    Nat Genet. 1997 May;16(1):68-73 PMID: 9140397
  9. Renal cancer in families with hereditary renal cancer: prospective analysis of a tumor size threshold for renal parenchymal sparing surgery.
    J Urol. 1999 May;161(5):1475-9 PMID: 10210376
  10. Inherited susceptibility to uterine leiomyomas and renal cell cancer.
    Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3387-92 PMID: 11248088
  11. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels.
    Cancer Cell. 2011 Sep 13;20(3):315-27 PMID: 21907923
  12. The tuberous sclerosis complex.
    N Engl J Med. 2006 Sep 28;355(13):1345-56 PMID: 17005952
  13. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome.
    Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):393-400 PMID: 11927500
  14. Optimizing systemic therapy for metastatic renal cell carcinoma beyond the first-line setting.
    Urol Oncol. 2015 Dec;33(12 ):538-45 PMID: 26482392
  15. Renal cell carcinoma.
    Lancet. 2009 Mar 28;373(9669):1119-32 PMID: 19269025
  16. Prevalence of microscopic lesions in grossly normal renal parenchyma from patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no renal disease: clinical implications.
    J Urol. 1995 Dec;154(6):2010-4; discussion 2014-5 PMID: 7500446
  17. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability.
    Cancer Cell. 2005 Aug;8(2):143-53 PMID: 16098467
  18. An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma.
    Cancer Cell. 2011 Oct 18;20(4):511-23 PMID: 22014576
  19. Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.
    Genome Res. 2012 Nov;22(11):2089-100 PMID: 23038766
  20. Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species.
    Mol Cell Biol. 2009 Aug;29(15):4080-90 PMID: 19470762
  21. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial.
    Clin Cancer Res. 2011 Jun 15;17(12):4071-81 PMID: 21525172
  22. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma.
    J Clin Oncol. 2013 Jan 10;31(2):181-6 PMID: 23213094
  23. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
    Cancer Cell. 2002 Aug;2(2):157-64 PMID: 12204536
  24. Nephron-sparing surgery for multifocal and hereditary renal tumors.
    Curr Opin Urol. 2014 Sep;24(5):466-73 PMID: 25014245
  25. Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas.
    Nat Genet. 1998 Sep;20(1):66-9 PMID: 9731534
  26. Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience.
    J Urol. 2001 Mar;165(3):777-81 PMID: 11176466
  27. Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys.
    J Natl Cancer Inst. 2008 Jan 16;100(2):140-54 PMID: 18182616
  28. Targeting the c-Met signaling pathway in cancer.
    Clin Cancer Res. 2006 Jun 15;12(12):3657-60 PMID: 16778093
  29. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America.
    Am J Hum Genet. 2003 Jul;73(1):95-106 PMID: 12772087
  30. Hereditary papillary renal cell carcinoma.
    J Urol. 1994 Mar;151(3):561-6 PMID: 8308957
  31. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C.
    Science. 1995 Sep 8;269(5229):1444-6 PMID: 7660130
  32. Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer.
    J Urol. 2007 Jun;177(6):2074-9; discussion 2079-80 PMID: 17509289
  33. Inhibition of transcription elongation by the VHL tumor suppressor protein.
    Science. 1995 Sep 8;269(5229):1402-6 PMID: 7660122
  34. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease.
    PLoS One. 2011;6(9):e23379 PMID: 21915260
  35. The genetic basis of kidney cancer: a metabolic disease.
    Nat Rev Urol. 2010 May;7(5):277-85 PMID: 20448661
  36. VHL, the story of a tumour suppressor gene.
    Nat Rev Cancer. 2015 Jan;15(1):55-64 PMID: 25533676
  37. The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1.
    Nephrol Dial Transplant. 2014 Jun;29(6):1203-10 PMID: 24729041
  38. Tuberous sclerosis.
    Lancet. 2008 Aug 23;372(9639):657-68 PMID: 18722871
  39. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
    N Engl J Med. 2016 Jan 14;374(2):135-45 PMID: 26536169
  40. Metabolism of kidney cancer: from the lab to clinical practice.
    Eur Urol. 2013 Feb;63(2):244-51 PMID: 23063455
  41. Non-clear cell renal cancer: disease-based management and opportunities for targeted therapeutic approaches.
    Semin Oncol. 2013 Aug;40(4):511-20 PMID: 23972715
  42. Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.
    Ann Oncol. 2011 Dec;22(12 ):2661-6 PMID: 22105611
  43. Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity.
    Eur Urol. 2015 Jan;67(1):85-97 PMID: 24857407
  44. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.
    Am J Surg Pathol. 2007 Oct;31(10):1578-85 PMID: 17895761
  45. Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer.
    J Urol. 2000 Feb;163(2):431-3 PMID: 10647647
  46. Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1).
    Biochem Soc Trans. 2015 Aug;43(4):650-6 PMID: 26551707
  47. Renal tumors in the Birt-Hogg-Dubé syndrome.
    Am J Surg Pathol. 2002 Dec;26(12):1542-52 PMID: 12459621
  48. Molecular diagnosis and therapy of kidney cancer.
    Annu Rev Med. 2010;61:329-43 PMID: 20059341
  49. Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial.
    Eur Urol. 2016 May;69(5):866-74 PMID: 26626617
  50. Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer.
    Cancer Cell. 2014 Dec 8;26(6):840-850 PMID: 25490448
  51. Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients.
    Am J Surg Pathol. 2014 Dec;38(12):1588-602 PMID: 25025441
  52. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial.
    Lancet. 2013 Mar 9;381(9869):817-24 PMID: 23312829
  53. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.
    Hum Mol Genet. 2005 Aug 1;14(15):2231-9 PMID: 15987702
Article Info
Journal
Current oncology reports
Abbr.
Curr Oncol Rep
ISSN
1534-6269
DOI
10.1007/s11912-016-0537-6
Email
abhinav.sidana@nih.gov
Published
2016-00-00
Pages
50
Language
English
Region
United States
NLM ID
100888967
Subset
IM
External Links
PubMed source DOI: 10.1007/s11912-016-0537-6 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2