TY - JOUR
T1 - Optimal treatment for metastatic bladder cancer
AU - Carballido, Estrella M.
AU - Rosenberg, Jonathan E.
PY - 2014/9
Y1 - 2014/9
N2 - Metastatic bladder cancer is a lethal disease. Cisplatin-based chemotherapy, including the combination regimens gemcitabine-cisplatin and methotrexate-vinblastine-doxorubicin-cisplatin, are the standard first-line therapies. Second-line therapies have modest activity and no significant improvement in patient outcomes. Agents targeting growth, survival, and proliferation pathways have been added to cytotoxic therapy with limited added benefit to date. Modulating host immune response to cancer-associated antigens appears promising, with multiple new therapeutic approaches being pursued. Next-generation sequencing of invasive urothelial carcinoma has provided insights into the biology of this disease and potential actionable targets. Alterations in the receptor tyrosine kinase/Ras pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway represent potential therapeutic targets in advanced disease, and novel agents are in development. Recent data from the Cancer Genome Atlas Research Network bladder cancer cohort and other efforts suggest that mutations in chromatin-regulatory genes are very common in invasive bladder tumors, and are more frequent than in other studied tumors. The discovery of new genomic alterations challenges drug development to change the course of this disease.
AB - Metastatic bladder cancer is a lethal disease. Cisplatin-based chemotherapy, including the combination regimens gemcitabine-cisplatin and methotrexate-vinblastine-doxorubicin-cisplatin, are the standard first-line therapies. Second-line therapies have modest activity and no significant improvement in patient outcomes. Agents targeting growth, survival, and proliferation pathways have been added to cytotoxic therapy with limited added benefit to date. Modulating host immune response to cancer-associated antigens appears promising, with multiple new therapeutic approaches being pursued. Next-generation sequencing of invasive urothelial carcinoma has provided insights into the biology of this disease and potential actionable targets. Alterations in the receptor tyrosine kinase/Ras pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway represent potential therapeutic targets in advanced disease, and novel agents are in development. Recent data from the Cancer Genome Atlas Research Network bladder cancer cohort and other efforts suggest that mutations in chromatin-regulatory genes are very common in invasive bladder tumors, and are more frequent than in other studied tumors. The discovery of new genomic alterations challenges drug development to change the course of this disease.
KW - Immunotherapeutics
KW - Metastatic bladder cancer
KW - Molecularmarkers
KW - Targeted therapies
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84904525746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904525746&partnerID=8YFLogxK
U2 - 10.1007/s11912-014-0404-2
DO - 10.1007/s11912-014-0404-2
M3 - Comment/debate
C2 - 25056737
AN - SCOPUS:84904525746
SN - 1523-3790
VL - 16
JO - Current oncology reports
JF - Current oncology reports
IS - 9
M1 - 404
ER -