Abstract:In recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody–dru… Show more
“…TURBT/radiotherapy/chemotherapy is not comparable to radical cystectomy, though responses to treatment may be variable and sometimes barely predictable. Novel target treatment options have been introduced in the advanced setting of the disease, including anti-Fibroblast Growth Factor Receptor (FGFR) and immune checkpoint inhibitors (ICIs), as well as antibody–drug conjugates (ADCs) (see below) [ 4 ].…”
Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.
“…TURBT/radiotherapy/chemotherapy is not comparable to radical cystectomy, though responses to treatment may be variable and sometimes barely predictable. Novel target treatment options have been introduced in the advanced setting of the disease, including anti-Fibroblast Growth Factor Receptor (FGFR) and immune checkpoint inhibitors (ICIs), as well as antibody–drug conjugates (ADCs) (see below) [ 4 ].…”
Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.
“…VOLGA trial is investigating perioperative combination therapy with EV and durvalumab with or without tremelimumab (anti-CTLA-4 antibody) for cisplatin-ineligible MIBC patients. The perioperative role of EV combined with pembrolizumab was investigated in phase 3 trials, particularly KEYNOTE-095/EV-303 trial in cisplatin-ineligible patients and KEYNOTE-B15/EV-304 trial in cisplatin-eligible MIBC patients [ 24 ].…”
Section: Evolving Paradigm Of Perioperative Treatment For Mibcmentioning
confidence: 99%
“…Immune checkpoint inhibitors (ICIs) including anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies [ 21 22 23 ], fibroblast growth factor receptor 3 inhibitors, and antibody-drug conjugates (ADCs) [ 24 ] have recently been introduced into therapeutic landscape of locally advanced or metastatic BC, and their promising clinical benefits against platinum-resistant BC have been validated through multiple large randomized clinical trials (RCTs). Several studies researching the perioperative roles of ICIs and ADCs are ongoing [ 24 25 26 ]. Herein, we discuss the current status and future perspectives of perioperative systemic strategies for MIBC.…”
Bladder cancer ranks as the 10th most common cancer type globally, and muscle-invasive disease accounts for approximately 25% of newly diagnosed bladder cancers. Despite definitive treatment, 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastasis within 2 years, leading to death. Perioperative systemic therapy is generally recommended to control local relapse or distant metastasis after surgical resection for patients with MIBC. Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard treatment to improve oncologic control and survival outcomes. Adjuvant chemotherapy is recommended for patients with pathological T3-4 or positive lymph nodes after radical cystectomy if no neoadjuvant chemotherapy was given. Nonetheless, perioperative systemic therapy is not applied widely because of its toxicity, and less than 25% of patients receive cisplatin-based neoadjuvant chemotherapy. Therefore, the development of predictive biomarkers for neoadjuvant chemotherapy efficacy and alternative effective regimens for cisplatin-ineligible patients are important. Furthermore, recently, novel anticancer agents such as immune checkpoint inhibitors and antibody-drug conjugates have proven survival benefits in the metastatic setting, thereby expanding their therapeutic applications to the perioperative setting for non-metastatic MIBC. Herein, we discuss the current status and future perspectives of perioperative systemic strategies for MIBC.
“…1 , ICIs as a monotherapy enhance the immune system’s ability to kill tumor cells [ 10 ], while ADCs as a monotherapy directly target and eliminate tumor cells [ 15 ]. The combined use of ADCs and ICIs has a synergistic effect, which can enhance the therapeutic effects of each [ 16 ]. Fig.…”
With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
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