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Why is precision medicine complicated in prostate cancer?


Why Is Genotypic Precision Medicine Challenging in Advanced Prostate Cancer?

Ulka Vaishampayan, MBBS, FAB

Dr. Vaishampayan examines the challenges associated with traditional genotypic precision medicine that underscore the need for novel approaches to increase and simplify the use of precision medicine in advanced prostate cancer.


Precision medicine has traditionally relied on genetic biomarkers to enable clinical decision making.1,2 However, the use of genotypic biomarkers in advanced prostate cancer is challenging because of the complexity and heterogeneity of the disease.3-7

Heterogeneity in advanced prostate cancer presents at several levels:

 

Heterogeneity levels in advanced prostate cancer: patient, tumor, cellular, hormonal, molecular

 

 

The heterogeneity of advanced prostate cancer has been attributed to 2 components3-6,13:

  1. Genomic instability of advancing disease
  2. Treatment-induced selective pressures, which can lead to genetic mutations and resistance
Two main components of advanced prostate cancer heterogeneity in primary tumor

 

 

AR, androgen receptor.

Due to the heterogeneity of prostate cancer, few widespread driver mutations have been identified, further complicating the use of genotypic precision medicine.17,18

Taken together, the heterogeneity of advanced disease and lack of widespread driver mutations underlie the need for novel precision medicine approaches in prostate cancer, such as the use of phenotypic biomarkers.19,20

Learn more:

 

References

1. Malik A et al. Front Oncol. 2019;9:1263. 2. Ku SY et al. Nat Rev Urol. 2019;16(11):645-654. 3. Magi-Galluzzi C et al. Mod Pathol. 1997;10(8):839-845. 4. Li L et al. Sci Signal. 2015;7(326):ra47. 5. Visakorpi T et al. Nat Genet. 1995;9(4):401-406. 6. Koivisto P et al. Cancer Res. 1997;57:314-319. 7. Friedlander TW et al. Am Soc Clin Oncol Educ Book. 2017;37:358-369. 8. Ren G et al. Genes Chromosomes Cancer. 2012;51(11):1014-1023. 9. Miyagi Y et al. Mod Pathol. 2010;23(11):1492-1498. 10. Barbieri CE et al. Nat Genet. 2013;44(6):685-689. 11. Svennson MA et al. Lab Invest. 2011;91(3):404-412. 12. Mehra R et al. Cancer Res. 2007;67(17):7991-7995. 13. van Dessel LF et al. Nat Commun. 2019;10(1):5251. 14. Maia MC et al. Nat Rev Urol. 2020;17(5):271-291. 15. Antonarakis ES et al. N Engl J Med. 2014;371(11):1028-1038. 16. Carrerira S et al. Sci Transl Med. 2014;6(254):254ra125. 17. Armenia J et al. Nat Genet. 2018;50(5):645-651. 18. Zehir A et al. Nat Med. 2017;23(6):703-713. 19. Kulkarni HR et al. Br J Radiol. 2018;91:20180308. 20. Abou D et al. Front Oncol. 2020;10:884.



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