New emerging targets in advanced urothelial carcinoma: Is it the primetime for personalized medicine?

Immune Checkpoint Inhibitors and Long-term Survival of Patients With Metastatic Urothelial Cancer

“…We identified 6 clinical trials evaluating pembrolizumab, avelumab, and nivolumab in the first-line, maintenance, and salvage settings for mUC; only treatments that received and have ongoing approvals from the US Food and Drug Administration (FDA) were included. Published articles of completed clinical trials were reviewed to determine the median age, sex, follow-up time, OS, PFS, objective response rates, and complete response rates within the treatment groups . The numbers at risk, which signify the most reliable indicator of long-term survival, among the treated cohorts within each clinical trial were tabulated at baseline and 12, 24, 36, and 48 months of follow-up.…”

“…Published articles of completed clinical trials were reviewed to determine the median age, sex, follow-up time, OS, PFS, objective response rates, and complete response rates within the treatment groups. 4 The numbers at risk, which signify the most reliable indicator of long-term survival, among the treated cohorts within each clinical trial were tabulated at baseline and 12, 24, 36, and 48 months of follow-up. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.…”

Biological and Exploitable Crossroads for the Immune Response in Cancer and COVID-19

“…Targeting the PD-1/PD-L1 axis —The first clinical application of anti-PD-1 in cancer has represented a true breakthrough [ 192 ] and, since then, the PD-1/PD-L1 axis blockade has become an approved therapeutic strategy in several cancer types, representing an unprecedented advancement in cancer treatment, as single agents or in combination with other anticancer agents [ 193 ]. Moreover, in recent years, immune checkpoint blockade has progressively been moved from late disease stages to the first-line setting, acknowledging its dramatic impact on patients’ prognosis in various cancer types, among which non-small cell lung cancer [ 194 ], melanoma [ 195 ], urothelial carcinoma [ 196 ] represent pioneering settings. As above mentioned, the PD-1/PD-L1 axis is a major player in immune exhaustion in COVID-19 infection, and lymphocytic PD-1 expression levels correlate with disease severity in patients affected by SARS-CoV-2.…”

Hypoxia inducible factor‐1 activator munc‐18‐interacting protein 3 promotes tumour progression in urothelial carcinoma

“…However, recently, the introduction of multiple agents targeting immune and oncogenic signalling pathways has changed substantially the treatment strategies for UC. For example, immune checkpoint inhibitors (ICIs), programmed cell death protein 1 inhibitors or programmed death‐ligand 1 inhibitor, have been administered as frontline, second‐line, or maintenance therapies, 3 demonstrating better outcomes than chemotherapy 4 . However, the median objective response rate of ICIs remains approximately 21% 5 .…”

“…For example, immune checkpoint inhibitors (ICIs), programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitor, have been administered as frontline, second-line, or maintenance therapies, 3 demonstrating better outcomes than chemotherapy. 4 However, the median objective response rate of ICIs remains approximately 21%. 5 Recently, molecular-targeted agents such as fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors and as an advanced type of agent, anti-nectin 4 antibody-drug conjugates (ADC), have been approved for UC.…”