Page 21 - Read Online
P. 21
Maitland Prostate cancer: from bench to bedside
improvements in survival. We will still be unable to DECLARATIONS
determine which patients will benefit, without detailed
longitudinal study of clinical tissues. Artificial cell line Authors’ contributions
models of “progression” help little in this regard. I N.J. Maitland contributed solely to the paper.
firmly believe that the future of cancer treatment lies
in a patient/tumor-specific strategy, and without the Financial support and sponsorship
clinical material to back this up, from both an early I wish to acknowledge the ongoing support of my
stage in the treatment cycle, and after the almost research in this area by grants from Prostate Cancer
inevitable relapse, we are limiting our understanding UK and Charity Soul.
of the disease. Every man appears to be different
in his responses, although there are some over- Conflicts of interest
arching changes in response to therapy. The “fatal There are no conflicts of interest.
lesion” provided at rapid autopsy has been a goal of
some major centers in the USA. This is an expensive Patient consent
exercise, which often lacks both pre-treatment normal Not applicable.
tissues (chemotherapy affects all tissues in the patient,
so a blood draw of lymphocytes from a patient after Ethics approval
extensive chemotherapy will reflect the populations Not applicable.
which survived the treatment) and the treatment
naïve cancers as comparators. The depth of analysis REFERENCES
of which we are now capable, simply demands better
tissues to be used to their fullest capacity. It is these 1. Chen W, Dong J, Haiech J, Kilhoffer MC, Zeniou M. Cancer stem
very tumor biopsies, which scientists really require cell quiescence and plasticity as major challenges in cancer therapy.
Stem Cells Int 2016;2016:1740936.
from the oncology community, not just from patients 2. Frame FM, Pellacani D, Collins AT, Simms MS, Mann VM,
referred to large research centers, but the “every Jones GD, Meuth M, Bristow RG, Maitland NJ. HDAC inhibitor
prostate cancer patient” samples, from truly standard confers radiosensitivity to prostate stem-like cells. Br J Cancer
of care environments. 2013;109:3023-33.
3. MacRae EJ, Giannoudis A, Ryan R, Brown NJ, Hamdy FC, Maitland
CONCLUSION N, Lewis CE. Gene therapy for prostate cancer: current strategies and
new cell-based approaches. Prostate 2006;66:470-94.
4. Gleason DF. Classification of prostatic carcinomas. Cancer
For almost 40 years, a limited set of established Chemother Rep 1966;50:125-8.
prostate cancer cell lines have dominated basic 5. Epstein JI. An update of the Gleason grading system. J Urol
research in prostate cancers. Whilst they retain a 2010;183:433-40.
number of key properties of the cancer in patients, they 6. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading
represent prostate cancer in an era before androgen Committee. The 2005 International Society of Urological Pathology
therapies and targeted radiotherapy. In addition, (ISUP) Consensus Conference on Gleason grading of prostatic
the cells from LNCaP, DU145 and PC3 have been 7. carcinoma. Am J Surg Pathol 2005;29:1228-42.
Gleason DF. Histologic grading of prostate cancer: a perspective.
passaged repeatedly in different growth media and in Hum Pathol 1992;23:273-9.
immune-compromised mouse hosts. To study prostate 8. Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JM,
cancer in the current decade we require models that Papaemmanuil E, Brewer DS, Kallio HM, Hognas G, Annala M,
represent contemporary disease. Kivinummi K, Goody V, Latimer C, O’Meara S, Dawson KJ, Isaacs
W, Emmert-Buck MR, Nykter M, Foster C, Kote-Jarai Z, Easton D,
By establishing a collaboration with the clinic, basic Whitaker HC; ICGC Prostate Group, Neal DE, Cooper CS, Eeles
scientists can begin to ask the correct questions, RA, Visakorpi T, Campbell PJ, McDermott U, Wedge DC, Bova GS.
The evolutionary history of lethal metastatic prostate cancer. Nature
whilst retaining the capacity to test mechanisms of 2015;520:353-7.
action or hypotheses in appropriate established cell 9. Huang J, Wang JK, Sun Y. Molecular pathology of prostate cancer
lines. However, we should be framing our hypotheses revealed by next-generation sequencing: opportunities for genome-
in actual cancers, either in human tissue biopsies or based personalized therapy. Curr Opin Urol 2013;23:189-93.
primary cell cultures (or both). Using multiple primary 10. Friedlander TW, Roy R, Tomlins SA, Ngo VT, Kobayashi Y, Azameera
cultures or biopsies is the equivalent of an in vitro A, Rubin MA, Pienta KJ, Chinnaiyan A, Ittmann MM, Ryan CJ, Paris
clinical trial for new drugs. Only by embracing the PL. Common structural and epigenetic changes in the genome of
castration-resistant prostate cancer. Cancer Res 2012;72:616-25.
heterogeneity of the prostate cancer patient population 11. Wyatt AW, Gleave ME. Targeting the adaptive molecular landscape of
can we begin to approach personalized, effective castration-resistant prostate cancer. EMBO Mol Med 2015;7:878-94.
cancer medicine with an ultimate goal of long-term 12. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg
treatments for men with prostate cancer. M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R,
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ November 17, 2017 269