Adenocarcinoma of the Prostate: Molecular Strategies for Improving the Therapeutic outcome for Radiation Therapy

Main Article Content

Tao Wang, PhD Brian Lewis, PhD Marcus Ruscetti, PhD Eric Ko, MD/PhD Paul Rava, MD/PhD Thomas J. FitzGerald, MD

Abstract

With process improvements in treatment including image guidance and intensity modulation, radiation therapy remains an important component of care for patients affected with prostate carcinoma. Although radiation therapy coupled with hormone therapy can provide exceptional cure rates in patients with low and intermediate risk factors, more progress is needed for patients with high risk of failure. These patients often can present with large volume disease in the prostate with unfavorable Gleason grade and risk for disease at and beyond the prostate capsule. These patients are predominantly treated with radiation therapy for local treatment. Developing strategies to augment control with radiation therapy in parallel to hormone therapy is important for the next generation of prostate cancer patients. This paper reviews potential molecular pathways that can sensitize prostate cancer cells to radiation therapy and potentially improve the therapeutic index for patients with this disease.

Article Details

How to Cite
WANG, Tao et al. Adenocarcinoma of the Prostate: Molecular Strategies for Improving the Therapeutic outcome for Radiation Therapy. Medical Research Archives, [S.l.], v. 9, n. 5, may 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2420>. Date accessed: 21 nov. 2024. doi: https://doi.org/10.18103/mra.v9i5.2420.
Section
Research Articles

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
2. Wo JY, Zietman AL. Why does androgen deprivation enhance the results of radiation therapy? Urol Oncol. 2008;26(5):522-529.
3. Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 2009;9(8):537-549.
4. Wang T, Languino LR, Lian J, Stein G, Blute M, Fitzgerald TJ. Molecular targets for radiation oncology in prostate cancer. Front Oncol. 2011;1:17.
5. Wang T, Alavian MR, Goel HL, Languino LR, Fitzgerald TJ. Bicalutamide inhibits androgen-mediated adhesion of prostate cancer cells exposed to ionizing radiation. Prostate. 2008;68(16):1734-1742.
6. Alonzi R, Padhani AR, Taylor NJ, et al. Antivascular effects of neoadjuvant androgen deprivation for prostate cancer: an in vivo human study using susceptibility and relaxivity dynamic MRI. Int J Radiat Oncol Biol Phys. 2011;80(3):721-727.
7. Schmidt-Hansen M, Hoskin P, Kirkbride P, Hasler E, Bromham N. Hormone and radiotherapy versus hormone or radiotherapy alone for non-metastatic prostate cancer: a systematic review with meta-analyses. Clin Oncol (R Coll Radiol). 2014;26(10):e21-46.
8. Goel HL, Sayeed A, Breen M, et al. beta1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase 1. J Cell Physiol. 2013;228(7):1601-1609.
9. Lu H, Wang T, Li J, et al. alphavbeta6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor. Cancer Res. 2016;76(17):5163-5174.
10. Park CC, Zhang H, Kim S, Lee R, Bissell MJ. β1 Integrin inhibition enhances apoptosis post-ionizing radiation (IR) in breast cancer in 3 dimensional culture and in vivo. 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology. 2007;November 1, 2007.
11. Albert JM, Cao C, Geng L, Leavitt L, Hallahan DE, Lu B. Integrin αvβ3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models. Int J Radiat Oncol Biol Phys. 2006;65(5):1536-1543.
12. Simon EL, Goel HL, Teider N, Wang T, Languino LR, Fitzgerald TJ. High dose fractionated ionizing radiation inhibits prostate cancer cell adhesion and β1 integrin expression. Prostate. 2005;64(1):83-91.
13. Davis RJ. Transcriptional regulation by MAP kinases. Mol Reprod Dev. 1995;42(4):459-467.
14. Karin M. Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors. Curr Opin Cell Biol. 1994;6(3):415-424.
15. Guyton KZ, Spitz DR, Holbrook NJ. Expression of stress response genes GADD153, c-jun, and heme oxygenase-1 in H2O2- and O2-resistant fibroblasts. Free Radic Biol Med. 1996;20(5):735-741.
16. Nickols NG, Nazarian R, Zhao SG, et al. MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer. Prostate Cancer Prostatic Dis. 2019;22(4):531-538.
17. Rodriguez-Berriguete G, Fraile B, Martinez-Onsurbe P, Olmedilla G, Paniagua R, Royuela M. MAP Kinases and Prostate Cancer. J Signal Transduct. 2012;2012:169170.
18. Ciccarelli C, Di Rocco A, Gravina GL, et al. Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo. J Cancer Res Clin Oncol. 2018;144(9):1685-1699.
19. Wang T, Carraway R, Chen H, Briggs J, FitzGerald TJ. ERK1 Mediated Epithelial-Mesenchumal Transition and Neuroendocrine Development in Prostate Cancer Cells that Survive High Dose Ionizing Radiation. International J of Radiation Oncology, Biology and Physics. 2012;84:S667-668.
20. Wang T, Carraway RE, LeRoche D, FitzGerald TJ. Disruption of ERK1/2 sensitizes radiation resistance prostate cancer cells to paclitaxel and ionizing radiation. International J of Radiation Oncology, Biology and Physics. 2014;90:S806.
21. Loenarz C, Coleman ML, Boleininger A, et al. The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens. EMBO Rep. 2011;12(1):63-70.
22. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270(3):1230-1237.
23. Bhandari V, Hoey C, Liu LY, et al. Molecular landmarks of tumor hypoxia across cancer types. Nat Genet. 2019;51(2):308-318.
24. Dhani N, Fyles A, Hedley D, Milosevic M. The clinical significance of hypoxia in human cancers. Semin Nucl Med. 2015;45(2):110-121.
25. Fraga A, Ribeiro R, Principe P, Lopes C, Medeiros R. Hypoxia and Prostate Cancer Aggressiveness: A Tale With Many Endings. Clin Genitourin Cancer. 2015;13(4):295-301.
26. Hompland T, Hole KH, Ragnum HB, et al. Combined MR Imaging of Oxygen Consumption and Supply Reveals Tumor Hypoxia and Aggressiveness in Prostate Cancer Patients. Cancer Res. 2018;78(16):4774-4785.
27. Stewart GD, Gray K, Pennington CJ, et al. Analysis of hypoxia-associated gene expression in prostate cancer: lysyl oxidase and glucose transporter-1 expression correlate with Gleason score. Oncol Rep. 2008;20(6):1561-1567.
28. Ambrosio MR, Di Serio C, Danza G, et al. Carbonic anhydrase IX is a marker of hypoxia and correlates with higher Gleason scores and ISUP grading in prostate cancer. Diagn Pathol. 2016;11(1):45.
29. Ranasinghe WK, Xiao L, Kovac S, et al. The role of hypoxia-inducible factor 1alpha in determining the properties of castrate-resistant prostate cancers. PLoS One. 2013;8(1):e54251.
30. Al-Ubaidi FL, Schultz N, Egevad L, Granfors T, Helleday T. Castration therapy of prostate cancer results in downregulation of HIF-1alpha levels. Int J Radiat Oncol Biol Phys. 2012;82(3):1243-1248.
31. Maeda A, Chen Y, Bu J, Mujcic H, Wouters BG, DaCosta RS. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1alpha Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model. Int J Radiat Oncol Biol Phys. 2017;97(1):184-194.
32. Schwartz DL, Bankson J, Bidaut L, et al. HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance. Mol Cancer Res. 2011;9(3):259-270.
33. Bharti SK, Kakkad S, Danhier P, et al. Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments. Neoplasia. 2019;21(2):239-246.
34. Bernardi R, Guernah I, Jin D, et al. PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR. Nature. 2006;442(7104):779-785.
35. Vergis R, Corbishley CM, Norman AR, et al. Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. Lancet Oncol. 2008;9(4):342-351.
36. D'Amours D, Desnoyers S, D'Silva I, Poirier GG. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999;342 ( Pt 2):249-268.
37. Grasso CS, Wu YM, Robinson DR, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487(7406):239-243.
38. Beltran H, Yelensky R, Frampton GM, et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013;63(5):920-926.
39. Nizialek E, Antonarakis ES. PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date. Cancer Manag Res. 2020;12:8105-8114.
40. Gani C, Coackley C, Kumareswaran R, et al. In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: An exploration of the therapeutic ratio. Radiother Oncol. 2015;116(3):486-494.
41. Hussain M, Carducci MA, Slovin S, et al. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Invest New Drugs. 2014;32(5):904-912.
42. Lloyd RL, Wijnhoven PWG, Ramos-Montoya A, et al. Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells. Oncogene. 2020;39(25):4869-4883.
43. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917-921.
44. Hussain M, Mateo J, Fizazi K, et al. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020;383(24):2345-2357.
45. Dungey FA, Loser DA, Chalmers AJ. Replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-Ribose) polymerase: mechanisms and therapeutic potential. Int J Radiat Oncol Biol Phys. 2008;72(4):1188-1197.
46. Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature. 2004;432(7015):316-323.