Priscilla Anderton

Introduction. Prostate cancer is the second most common cancer diagnosed in men world-wide.¹ The pathology is driven by genetic mutations, resulting in unregulated growth of the prostatic epithelial cells.¹ Initial treatment includes prostatectomy and androgen deprivation therapy.¹ Metastatic castration resistant prostate cancer (mCRPC) is cancer that progresses despite androgen ablation.¹ Due to the low survival rate of mCRPC patients, there is a need for new treatment options.² Researchers have turned their focus to the STEAP proteins – a family of four transmembrane proteins expressed in prostatic epithelial cells.³ STEAP1 and STEAP2 expression is upregulated in prostate cancer cells when compared to non-cancerous cells, leading researchers to believe they might serve as imaging or therapeutic targets for mCRPC patients.³  Methods. To assess the effects of STEAP1 knockdown on cell viability, researchers transfected LNCaP cells with a control siRNA and a STEAP1 knockdown siRNA.⁴  Researchers then subjected these cells to a Ki67 assay to assess cell growth.⁴ A TUNEL assay was then used with the transfected cells to measure STEAP1 knockdown impact on apoptosis.⁴ Researchers also assessed the effects of STEAP2 knockdown by treating PC3 cells with STEAP2 siRNA.³ iCelligence analysis was then used with the transfected cells to determine the effects on proliferation rate.³ The migratory potential was also measured using IBIDI cell cultures.³ Finally, researchers determined if anti-STEAP1 antibody could be used to localize mCRPC sites in soft tissue and bone. Nineteen mCRPC patients were administered radiolabeled 89Zr-DFO-MSTP2109A with a non-radiolabeled carrier and imaging results were confirmed with biopsy.⁵   Results. STEAP1 knockdown significantly decreased the viability and proliferation of LNCaP cells and increased their apoptosis.⁴ Similarly, STEAP2 knockdown significantly reduced the proliferation rate and final cell count of PC3 cells.³ In addition, STEAP2 knockdown significantly decreased the migratory potential of PC3 cells.³ Regarding imaging, researchers found that anti-STEAP1 antibody showed high-contrast localization in mCRPC at both bone and soft-tissue images in almost all patients.⁵   Conclusions. STEAP1 and STEAP2 are required for the survival, proliferation, and migration of prostate cancer cells.^3,4 As STEAP1 and STEAP2 are highly upregulated in prostate cancer cells, this warrants further investigation into the therapeutic use of these proteins in mCRPC patients. In addition, STEAP1 antibody may also serve as a diagnostic tool for mCRPC patients.⁵

1. Rebello RJ, Oing C, Knudsen KE, et al. Prostate Nat Rev Dis Primers. 2021;7(1):9. Published 2021 Feb 4. doi:10.1038/s41572-020-00243-0
2. Rosellini M, Santoni M, Mollica V, et Treating Prostate Cancer by Antibody-Drug Conjugates. Int J Mol Sci. 2021;22(4):1551. Published 2021 Feb 4. doi:10.3390/ijms22041551
3. Burnell SEA, Spencer-Harty S, Howarth S, et STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells. Scientific Reports. 2018;8(1):6252. doi:10.1038/s41598-018-24655-x
4. Gomes IM, Rocha SM, Gaspar C, et Knockdown of STEAP1 inhibits cell growth and
5. induces apoptosis in LNCaP prostate cancer cells counteracting the effect of androgens. Med Oncol. 2018;35(3):40. Published 2018 Feb 20. doi:10.1007/s12032-018-1100-0
6. Carrasquillo JA, Fine BM, Pandit-Taskar N, et al. Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using 89Zr-DFO-MSTP2109A Anti-STEAP1 J Nucl Med. 2019;60(11):1517-1523. doi:10.2967/jnumed.118.222844