TY - JOUR
T1 - Elevating the Horizon
T2 - Emerging Molecular and Genomic Targets in the Treatment of Advanced Urothelial Carcinoma
AU - Kurtoglu, Metin
AU - Davarpanah, Nicole N.
AU - Qin, Rui
AU - Powles, Thomas
AU - Rosenberg, Jonathan E.
AU - Apolo, Andrea B.
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Despite recent advances in the identification of genomic alterations that lead to urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas continue to have poor clinical outcomes. In the present review, we focus on targeted therapies that have yielded the most promising results alone or combined with traditional chemotherapy, including the antiangiogenesis agent bevacizumab, the human epidermal growth factor receptor 2 antibody trastuzumab, and the tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing clinical trials that use innovative approaches, including dose-dense scheduling of singular chemotherapy combinations, prospective screening of tumor tissues for mutational targets and biomarkers to predict chemosensitivity before the determination of the therapeutic regimen, and novel agents that target proteins in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD-1] and anti-PD-ligand 1) that have shown significant potential in preclinical models and early clinical trials. New agents and targeted therapies, alone or combined with traditional chemotherapy, will only be validated through accrual to developing clinical trials that aim to translate these therapies into individualized treatments and improved survival rates in urothelial carcinoma.
AB - Despite recent advances in the identification of genomic alterations that lead to urothelial oncogenesis in vitro, patients with advanced urothelial carcinomas continue to have poor clinical outcomes. In the present review, we focus on targeted therapies that have yielded the most promising results alone or combined with traditional chemotherapy, including the antiangiogenesis agent bevacizumab, the human epidermal growth factor receptor 2 antibody trastuzumab, and the tyrosine kinase inhibitor cabozantinib. We also describe ongoing and developing clinical trials that use innovative approaches, including dose-dense scheduling of singular chemotherapy combinations, prospective screening of tumor tissues for mutational targets and biomarkers to predict chemosensitivity before the determination of the therapeutic regimen, and novel agents that target proteins in the immune checkpoint regulation pathway (programmed cell death protein 1 [PD-1] and anti-PD-ligand 1) that have shown significant potential in preclinical models and early clinical trials. New agents and targeted therapies, alone or combined with traditional chemotherapy, will only be validated through accrual to developing clinical trials that aim to translate these therapies into individualized treatments and improved survival rates in urothelial carcinoma.
KW - Bladder cancer
KW - Clinical trials
KW - Immune checkpoints
KW - Novel agents
KW - Targeted therapy
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U2 - 10.1016/j.clgc.2015.02.009
DO - 10.1016/j.clgc.2015.02.009
M3 - Review article
AN - SCOPUS:84941599458
SN - 1558-7673
VL - 13
SP - 410
EP - 420
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 5
ER -