brain MRI image brain MRI image

Why Is Precision Medicine Complicated
in Prostate Cancer?

Precision medicine has traditionally utilised genetic biomarkers to enable clinical decision making.1-4
However, the use of genotypic biomarkers in advanced prostate cancer is challenging because of the complexity and heterogeneity of the disease.5-8

Heterogeneity in advanced prostate cancer presents at several levels:

Patient image

Patient9-11

Geographic and ethnic diversity

Environmental exposures

Tumor image

Tumour2,11-14

Primary vs metastatic tumours

Multifocal tumours that developed independently

Cellular image

Cellular11,15

Polyclonal origins within the same tumour

Patient image

Hormonal11,16

AR expression and resistance mechanisms

Castration sensitive vs castration resistant

Molecular image

Molecular11,17

Germline alterations

Somatic alterations

Genomic instability

AR, androgen receptor.

The heterogeneity in advanced prostate cancer has been attributed to two components5,18-20:

  1. Genomic instability of advancing disease5,18,20
  2. Treatment-induced selective pressures, which can lead to genetic mutations and resistance5,18,19

Primary Tumour

one two three four

Advancing
Disease and
Metastasis5,18,20

Selective Pressure
From Therapeutic
Interventions5,18,19

Image modified from Maia MC et al. Nat Rev Urol. 2020;17(5):271-291.

Advancing Disease
and Metastasis5,18,20

Selective Pressure From
Therapeutic Interventions5,18,19

Image modified from Maia MC et al. Nat Rev Urol. 2020;17(5):271-291.

Due to the heterogeneity in prostate cancer, few widespread mutations have been identified, further complicating the use of genotypic precision medicine.21,22

Taken together, the heterogeneity of advanced disease and the lack of widespread driver mutations underlie the need for novel precision medicine approaches in prostate cancer, such as the use of phenotypic biomarkers.23-26

References 1. Barbieri CE, Tomlins SA. Urol Oncol. 2014;32(1):53.e15-22. 2. Ku SY et al. Nat Rev Urol. 2019;16(11):645-654. 3. de Bono J et al. N Engl J Med. 2020;382(22):2091-2102. 4. Abida W et al. JAMA Oncol. 2019;5(4):471-478. 5. Testa U et al. Medicines (Basel). 2019;6(3):82. 6. Carm KT et al. Sci Rep. 2019;9(1):13579. 7. Mateo J et al. Nat Cancer. 2020;1(11):1041-1053. 8. Haffner MC et al. Nat Rev Urol. 2021;18(2):79-92. 9. Ren G et al. Genes Chromosomes Cancer. 2012;51(11):1014-1023. 10. Miyagi Y et al. Mod Pathol. 2010;23(11):1492-1498. 11. Boyd LK et al. Nat Rev Urol. 2012;9:652-664. 12. Friedlander TW et al. Am Soc Clin Oncol Educ Book. 2017;37:358-369. 13. Barbieri CE et al. Nat Genet. 2013;44(6):685-689. 14. Svensson MA et al. Lab Invest. 2011;91(3):404-412. 15. Mehra R et al. Cancer Res. 2007;67(17):7991-7995. 16. Koivisto P et al. Cancer Res. 1997;57(2):314-319. 17. Van Dessel LF et al. Nat Commun. 2019;10(1):5251. 18. Venkatesan S et al. Cold Spring Harb Perspect Med. 2017;7(8):a026617. 19. Li Q et al. Nat Commun. 2018;9(1):3600. 20. Karanika S et al. Oncogene. 2015;34(22):2815-2822. 21. Armenia J et al. Nat Genet. 2018;50(5):645-651. 22. The Cancer Genome Atlas Research Network. Cell. 2015;163(4):1011-1025. 23. Perera M et al. Eur Urol. 2020;77(4):403-417. 24. Kulkarni HR et al. Br J Radiol. 2018;91(1091):20180308. 25. Abou D et al. Front Oncol. 2020;10:884. 26. Tian S et al. Cancer Cell Int. 2020;20:409.
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