[Tyrosine Kinases in Soft Tissue Tumors]

Overview

Journal Pathologe

Specialty Pathology

Date 2014 Sep 7

PMID 25193679

Citations 12

Authors

T Knosel

E Kampmann

T Kirchner

A Altendorf-Hofmann

Affiliations

Soon will be listed here.

Abstract

The development of therapeutic agents that specifically target the molecular alterations critical for tumorigenesis has a tremendous impact on the management of cancer patients. The successful treatment of advanced gastrointestinal stromal tumors (GIST) with receptor tyrosine kinase (RTK) inhibitors has raised the hope that other malignancies could also benefit from a similar treatment. Tyrosine kinase receptors are promising targets for personalized medicine and new drugs are currently in phase 2 and phase 3 clinical trials. We analyzed a large cohort of soft tissue sarcomas for different tyrosine kinase receptors and correlated the results with clinicopathological parameters. A total of 275 soft tissue sarcomas from the Ludwig-Maximilians University (LMU) were revisited and catagorized according to the current World Health Organization (WHO) classification system. Different entities showed distinct survival curves in 10-year long-term survival. Furthermore, different subtypes of sarcomas showed distinct expression profiles at the protein level. The expression of vascular endothelial growth factor (VEGF) receptors is associated with tumor progression. Due to the fact that not all patients respond to RTK inhibitor therapy, protein signatures should be evaluated before targeting therapy to give a rationale for a viable personalized therapy.

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References

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Sorbye S, Kilvaer T, Valkov A, Donnem T, Smeland E, Al-Shibli K . Prognostic impact of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas. PLoS One. 2012; 7(10):e47068. PMC: 3465267. DOI: 10.1371/journal.pone.0047068. View

Tammela T, Enholm B, Alitalo K, Paavonen K . The biology of vascular endothelial growth factors. Cardiovasc Res. 2005; 65(3):550-63. DOI: 10.1016/j.cardiores.2004.12.002. View

Knosel T, Emde A, Schluns K, Chen Y, Jurchott K, Krause M . Immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer. Neoplasia. 2005; 7(8):741-7. PMC: 1501883. DOI: 10.1593/neo.05178. View

Gacche R, Meshram R . Angiogenic factors as potential drug target: efficacy and limitations of anti-angiogenic therapy. Biochim Biophys Acta. 2014; 1846(1):161-79. DOI: 10.1016/j.bbcan.2014.05.002. View

van der Graaf W, Blay J, Chawla S, Kim D, Bui-Nguyen B, Casali P . Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012; 379(9829):1879-86. DOI: 10.1016/S0140-6736(12)60651-5. View

Kilvaer T, Smeland E, Valkov A, Sorbye S, Bremnes R, Busund L . The VEGF- and PDGF-family of angiogenic markers have prognostic impact in soft tissue sarcomas arising in the extremities and trunk. BMC Clin Pathol. 2014; 14(1):5. PMC: 3898209. DOI: 10.1186/1472-6890-14-5. View

Knosel T, Altendorf-Hofmann A, Lindner L, Issels R, Hermeking H, Schuebbe G . Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier. J Clin Pathol. 2014; 67(7):592-8. DOI: 10.1136/jclinpath-2013-202106. View

Issels R, Lindner L, Verweij J, Wust P, Reichardt P, Schem B . Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010; 11(6):561-70. PMC: 3517819. DOI: 10.1016/S1470-2045(10)70071-1. View

10.

Folkman J . Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 1972; 175(3):409-16. PMC: 1355186. DOI: 10.1097/00000658-197203000-00014. View

11.

Abdeen A, Chou A, Healey J, Khanna C, Osborne T, Hewitt S . Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer. 2009; 115(22):5243-50. PMC: 7251638. DOI: 10.1002/cncr.24562. View

12.

Knosel T, Heretsch S, Altendorf-Hofmann A, Richter P, Katenkamp K, Katenkamp D . TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases. Eur J Cancer. 2010; 46(6):1170-6. DOI: 10.1016/j.ejca.2010.01.032. View

13.

Kilvaer T, Valkov A, Sorbye S, Smeland E, Bremnes R, Busund L . Profiling of VEGFs and VEGFRs as prognostic factors in soft tissue sarcoma: VEGFR-3 is an independent predictor of poor prognosis. PLoS One. 2010; 5(12):e15368. PMC: 3001883. DOI: 10.1371/journal.pone.0015368. View

14.

Fredriksson L, Li H, Eriksson U . The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev. 2004; 15(4):197-204. DOI: 10.1016/j.cytogfr.2004.03.007. View

15.

Ostman A . PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004; 15(4):275-86. DOI: 10.1016/j.cytogfr.2004.03.002. View

16.

Hamidov Z, Altendorf-Hofmann A, Chen Y, Settmacher U, Petersen I, Knosel T . Reduced expression of desmocollin 2 is an independent prognostic biomarker for shorter patients survival in pancreatic ductal adenocarcinoma. J Clin Pathol. 2011; 64(11):990-4. DOI: 10.1136/jclinpath-2011-200099. View

17.

Ranieri G, Mammi M, Di Paola E, Russo E, Gallelli L, Citraro R . Pazopanib a tyrosine kinase inhibitor with strong anti-angiogenetic activity: a new treatment for metastatic soft tissue sarcoma. Crit Rev Oncol Hematol. 2013; 89(2):322-9. DOI: 10.1016/j.critrevonc.2013.08.012. View

18.

Yonemori K, Tsuta K, Ando M, Hirakawa A, Hatanaka Y, Matsuno Y . Contrasting prognostic implications of platelet-derived growth factor receptor-β and vascular endothelial growth factor receptor-2 in patients with angiosarcoma. Ann Surg Oncol. 2011; 18(10):2841-50. DOI: 10.1245/s10434-011-1640-4. View