Antibody-Drug Conjugates in Urothelial Carcinomas

Sarfaty, Michal; Rosenberg, Jonathan E.

doi:10.1007/s11912-020-0879-y

Cited by 24 publications

(23 citation statements)

References 41 publications

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“…However, patients with high sPD-L1 are at higher risk under both platinum and ICI therapy and might therefore benefit from other therapy modalities. Therefore, further research should answer the question whether locally progressed and/or metastatic MIBC patients with high sPD-L1 levels may better benefit from targeted therapies (e.g., anti-FGFR, nectin-4 targeted or the currently approved sacituzumab govitecan) [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

High Serum PD-L1 Levels Are Associated with Poor Survival in Urothelial Cancer Patients Treated with Chemotherapy and Immune Checkpoint Inhibitor Therapy

Krafft

Oláh

Reis

et al. 2021

Cancers

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Serum PD-L1 (sPD-L1) levels are associated with prognosis in various tumors but has not yet been investigated in advanced bladder cancer. We assessed pretreatment serum samples from 83 BC patients who received platinum chemotherapy and from 12 patients who underwent immune checkpoint inhibitor (ICI) therapy. In addition, on-treatment samples from further therapy cycles were collected during chemotherapy (n = 58) and ICI therapy (n = 11). Serum PD-L1 levels were determined using ELISA. High baseline sPD-L1 levels were associated with worse ECOG status (p = 0.007) and shorter overall survival for both chemotherapy- and ICI-treated patients (p = 0.002 and p = 0.040, respectively). Multivariate analysis revealed high baseline sPD-L1 level as an independent predictor of poor survival for platinum-treated patients (p = 0.002). A correlation analysis between serum concentrations of PD-L1 and matrix metalloprotease-7 (MMP-7)—a protease which was recently found to cleave PD-L1—revealed a positive correlation (p = 0.001). No significant sPD-L1 changes were detected during chemotherapy, while in contrast we found a strong, 25-fold increase in sPD-L1 levels during atezolizumab treatment. In conclusion, our work demonstrates that pretreatment sPD-L1 levels are associated with a poor prognosis of BC patients undergoing platinum and ICI therapy. Future research should prospectively address the value of sPD-L1 in predicting treatment response.

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Section: Discussionmentioning

confidence: 99%

High Serum PD-L1 Levels Are Associated with Poor Survival in Urothelial Cancer Patients Treated with Chemotherapy and Immune Checkpoint Inhibitor Therapy

Krafft

Oláh

Reis

et al. 2021

Cancers

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“…Another interesting emerging class for the treatment for metastatic UC is antibody-drug conjugate (ADC), that consists in monoclonal antibody against a target expressed on cancer cell bounded to a cytotoxic agent with a protease-cleavable or non-cleavable linker [75]. When the monoclonal antibody binds to a tumor antigen, the drug is internalized and the active chemotherapeutic agent is released into the selected cells, leading to cell death.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

Mollica

Rizzo

Montironi

et al. 2020

Cancers

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Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.

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“…MMAE is also the payload in enfortumab vedotin, approved by the FDA in 2019 for the treatment of patients with locally advanced or metastatic urothelial cancer who had received a prior programmed cell death (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy regimen [146]. Here, the antibody targets Nectin-4, a cell surface protein involved in Ca 2+ -independent cellular adhesion, expressed in urothelial cancer cells [37].…”

Section: Peptide Derivativesmentioning

confidence: 99%

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

et al. 2020

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The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

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Antibody-Drug Conjugates in Urothelial Carcinomas

Cited by 24 publications

References 41 publications

High Serum PD-L1 Levels Are Associated with Poor Survival in Urothelial Cancer Patients Treated with Chemotherapy and Immune Checkpoint Inhibitor Therapy

High Serum PD-L1 Levels Are Associated with Poor Survival in Urothelial Cancer Patients Treated with Chemotherapy and Immune Checkpoint Inhibitor Therapy

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

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