Metastatic urothelial carcinoma (UC) carries a poor prognosis and a 5-year overall survival of less than 5%, despite standard of care therapy using cisplatin-based chemotherapy and immune checkpoint inhibitors. Thus, novel agents that improve survival and have an acceptable toxicity profile are urgently needed. Antibody-drug conjugates (ADCs) represent a promising new treatment option that utilizes the targeting ability of an antibody to deliver cytotoxic drugs directly to tumors. Many ADCs are currently being investigated for treatment of UC, with enfortumab vedotin being recently approved by the US Food and Drug Administration for treatment of metastatic UC with progressive disease after chemotherapy and/or immune checkpoint inhibitors. Overall, ADCs hold promise as a long-awaited treatment option for UC.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.clgc.2020.11.006 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.
Antibody-drug conjugates (ADCs) have emerged as a promising strategy in targeted cancer therapy, enabling the precise delivery of cytotoxic agents to tumor sites while minimizing systemic toxicity. However, traditional ADCs face significant limitations, including restricted drug loading capacity, where an optimal drug-to-antibody ratio (DAR) is crucial; low DARs may lead to insufficient potency, while high DARs can cause rapid clearance and increased toxicity. Additionally, ADCs often suffer from instability in circulation due to the potential for premature release of cytotoxic agents, resulting in off-target effects and reduced therapeutic efficacy.
View Article and Find Full Text PDFSci Adv
January 2025
The Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).
View Article and Find Full Text PDFMol Ther Oncol
September 2024
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.
View Article and Find Full Text PDFGland Surg
December 2024
Medical Imaging Department, Affiliated Hospital of Jining Medical University, Jining, China.
Background: Breast cancer is the most common malignant tumor among women, with an increasing incidence each year. The subtypes of human epidermal growth factor receptor 2 (HER2)-negative breast cancer, classified as HER2-low and HER2-zero based on HER2 receptor expression, show differences in clinical characteristics, therapeutic approaches, and prognoses. Distinguishing between these subtypes is clinically valuable as it can impact treatment strategies, including the use of next-generation antibody-drug conjugates (ADCs) targeting HER2-low tumors.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!