Clinical Genitourinary Cancer, Journal Year: 2024, Volume and Issue: unknown, P. 102278 - 102278
Published: Nov. 1, 2024
Language: Английский
Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(11), P. 2089 - 2108
Published: Oct. 23, 2024
Abstract Antibody–drug conjugates (ADC) represent one of the most rapidly expanding treatment modalities in oncology, with 11 ADCs approved by FDA and more than 210 currently being tested clinical trials. Spanning over 40 years, ADC development has enhanced our understanding multifaceted mechanisms action for this class therapeutics. In article, we discuss key insights into toxicity, efficacy, stability, distribution, fate ADCs. Furthermore, highlight ongoing challenges related to their optimization, rational sequencing strategies, identification predictive biomarkers. Significance: The utilization have allowed relevant improvements prognosis multiple cancer types. Concomitantly, rise oncology produced several challenges, including prediction activity, sequence, minimization side effects, that still too often resemble those cytotoxic molecule they carry. review, retrace years field delve deep these complex therapeutics reasons behind many achievements failures observed date.
Language: Английский
Citations
17
Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14
Published: Jan. 29, 2025
Objective This study aimed to determine and compare the tumor shrinkage rate its durability by enfortumab vedotin treatment between primary urothelial carcinoma metastatic organs. Methods We retrospectively evaluated in 39 Japanese patients treated with for advanced carcinoma. also periods of maintenance (the period when best response was maintained) regrowth from growth confirmation) Results Measurable organs included lung 17, lymph node 22, liver 6, bone 5 cases. Primary lesion detected 20 The mean rates lung, node, liver, metastases sites were 21% (−212 100), 13% (−130 86), −8.5% (−158 85), −64% (−250 21), 22% (−38 79), respectively. maintained 5.9 (0.7–14) months metastases, 8.3 (2.6–14.5) 3.6 0.7 1.8 (0.7–5.4) sites, 7.3 (2.2–19.4), 4.8 (2.0–8.9), 2.8, 6.5, 2.5 (1.1–5.9) months, Conclusions Enfortumab showed significant tumor, whereas limited tumor.
Language: Английский
Citations
1
BJU International, Journal Year: 2024, Volume and Issue: 134(4), P. 615 - 621
Published: June 19, 2024
Objective To evaluate the potential utility of antibody‐drug conjugates targeting trophoblast cell surface antigen‐2 (TROP‐2) in patients with primary penile squamous carcinoma (PSCC), recurrence (REC cohort), and patient‐matched distant metastases (MET to assess use TROP‐2 as a predictive non‐invasive biomarker PSCC. Methods A cohort comprising PRIM ( n = 37), REC 5) MET subcohort 7), including lymph node lung metastases, was analysed using quantitative real‐time PCR, ELISA immunohistochemical staining evaluation H‐score. Results mRNA serum protein levels were significantly increased recurrent PSCC compared cancer‐free controls (both P < 0.001). Immunohistochemical analysis revealed that most 34/37, median H‐score 260, interquartile range [IQR] 210–300), well all (median 200 [165–290]) cohorts 280 [260–300]) exhibited moderate strong membranous expression. Additionally, The (membranous expression) positively correlated ρ 0.69, 0.0001, R 2 0.70) 0.86, 0.59), indicating its Conclusion In summary, our results support further studies on diagnostic therapeutic target primary, metastatic
Language: Английский
Citations
4
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(14)
Published: July 1, 2024
Abstract Antibody‐drug conjugates (ADCs) represent a novel type of targeted cancer therapy combining the specificity monoclonal antibodies with cytotoxicity conventional chemotherapy. Recently, ADCs have demonstrated practice‐changing efficacy across diverse solid cancers. The anti‐NECTIN‐4 ADC enfortumab vedotin (EV) has just been approved for patients urothelial and is currently under investigation castration‐resistant prostate (CRPC e.g. Phase II ENCORE trial). Our objective was to evaluate EV in established (PCa) cell lines examine membranous NECTIN‐4 expression primary tumours (PRIM) distant metastases (MET). heterogeneously expressed panel PCa lines. led growth inhibition expressing cells (22Rv1 LNCaP), whereas NECTIN‐4‐negative PC‐3 were significantly less responsive EV, emphasizing dependence response on its target expression. Immunohistochemical staining revealed moderate only small subgroup CRPC lung peritoneal MET [ n = 3/22 H‐score ≥100, median 140 (IQR 130–150)], while 100% PRIM ( 48/48) 86.4% common sites 19/22), including lymph node, bone liver MET, negative. In summary, may be effective NECTIN‐4‐positive PCa. However, our findings demonstrate that tumoural predominantly low metastatic PCa, which suggests biomarker‐stratified subgroup.
Language: Английский
Citations
4
Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 180 - 180
Published: Jan. 29, 2025
The emergence of antibody–drug conjugates (ADCs) has transformed the treatment landscape a variety cancers. ADCs typically consist three main components: monoclonal antibody, chemical linker, and cytotoxic payload. These integrated therapeutic modalities harness benefits each component to provide response that cannot be achieved by conventional chemotherapy. Antibodies play roles in determining tumor specificity through target-mediated uptake, prolonging circulation half-life payloads, providing additional mechanisms action inherent original thus significantly contributing overall performance ADCs. However, have unique safety concerns, such as drug-induced adverse events related uptake ADC normal tissues (so-called “on-target, off-tumor toxicity”) platform toxicity, which are partially derived from limited antibodies. Identifying suitable target antigens impacts clinical success requires careful consideration, given multifaceted aspects this modality. This review briefly summarizes representative antibodies efficacy Key considerations for selecting cell surface therapy also highlighted.
Language: Английский
Citations
0
American Society of Clinical Oncology Educational Book, Journal Year: 2025, Volume and Issue: 45(2)
Published: Jan. 1, 2025
Antibody-drug conjugates (ADCs) represent an emerging class of therapeutics across solid tumor oncology and are already positioned as a cornerstone therapy for patients with urothelial carcinoma (UC). In recent years, there has been paradigm shift in the therapeutic landscape frontline treatment UC formerly relied on use platinum-based agents now evolved to include combination strategies ADCs. These dramatic changes due part our improved understanding molecular features bladder tumors identification tumor-associated antigens specific UC, which may serve druggable targets. Despite notable advances clinical success ADCs other malignancies, their full potential remains largely unmet. Early enfortumab vedotin sacituzumab govitecan demonstrated antitumor activity; however, multiple challenges these ADCs, including on-target, off-tumor toxicity difficulty maintaining sustained responses. Newer-generation ADC constructs, either alone or approaches, currently under investigation. This review examines historical development, current landscape, trends highlighting both progress made obstacles that continue hinder optimal outcomes.
Language: Английский
Citations
0
Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 134, P. 102900 - 102900
Published: Feb. 10, 2025
The treatment landscape for patients with advanced urothelial carcinoma (UC) has evolved rapidly in recent years. In current guidelines, combination enfortumab vedotin plus pembrolizumab is the first-line (1L) standard of care, and other recommended 1L options are platinum-based chemotherapy followed by avelumab as switch-maintenance without progression, or nivolumab, cisplatin, gemcitabine cisplatin-eligible only. Individual differ terms their health status, disease characteristics, expected toxicities, preferences; thus, a "one-size-fits-all" approach to unlikely be optimal. availability several creates potential individualized treatment. this review, we discuss factors that may considered when selecting UC, including efficacy safety data from phase 3 trials real-world studies, quality life, patient priorities treatment, sequencing, biomarkers, access cost. Patients physicians should benefit-risk balance all available enable shared decision-making. Longer follow-up clinical additional studies needed further inform selection.
Language: Английский
Citations
0
Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(2)
Published: Feb. 10, 2025
Desmoplastic small round cell tumor is a rare sarcoma type with poor prognosis for which there no standard of care. It primarily affects adolescents and young adults treatment both multimodal challenging due to the aggressive nature disease. we describe case 27-year-old male who presented hematuria five-centimeter mass on his bladder wall. His details an especially diagnosis as pathology IHC raised suspicion poorly differentiated urothelial carcinoma until next-generation sequencing revealed ESWR1::WT1 fusion gene rearrangement pathognomonic desmoplastic tumor. After failing multiple lines chemotherapy also pembrolizumab, patient was started enfortumab-vedotin (EV), antibody-drug conjugate targeting Nectin-4. Patient sustained partial response documented disease control clinical benefit 23 months. Later, staining nectin-4 found be moderately positive. This report first usage EV in management gives light new potential therapeutic strategy this
Language: Английский
Citations
0
Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 333 - 333
Published: Feb. 24, 2025
Despite recent advances in cancer treatment, the prognosis for uterine malignancies (carcinoma and sarcoma) requires further improvement. Antibody-drug conjugates (ADCs) have emerged as a novel class of anti-cancer therapeutic agents, multiple ADCs been approved other types cancer. In 2024, trastuzumab deruxtecan received approval from US Food Drug Administration became first ADC treatment malignancies. Many are currently being investigated malignancies, therefore, there is need to gain deeper understanding ADCs. this article, we aim provide comprehensive overview advancements The contents article include structure mechanism action, an analysis clinical trials, expected future questions. This also focuses on sarcoma, which not often highlighted target treatment.
Language: Английский
Citations
0
Modern Pathology, Journal Year: 2025, Volume and Issue: unknown, P. 100753 - 100753
Published: March 1, 2025
Muscle-invasive bladder cancer (MIBC) presents significant treatment challenges. Antibody-drug conjugates (ADCs) targeting HER2, TROP-2, and NECTIN4 offer promising therapeutic options. This study examined the spatial expression of in MIBC metastases, their association with molecular subtypes, clinical outcomes. Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 251 patients were analyzed using immunohistochemistry microarrays (TMA). Expression patterns between tumor front (TF) center (TC) compared, statistical analyses assessed associations subtypes parameters. Additionally, 67 matched lymph node metastases a secondary cohort comprising 16 distant including seven primary tumors, to explore advanced stages. In HER2 was predominantly negative (83%) but showed higher positivity TC. TROP-2 exhibited high overall (58% score 3+), while displayed heterogeneity stronger Spatial overexpression at relative associated better disease free survival. Accurate assessment required four biopsies for three TROP-2. urothelial-like genomically unstable whereas widely expressed except mesenchymal-like subtype. absence staining basal, mes-like Sc/Nec-like subtypes. Paired scores all markers, reduced expression. revealed considerable compared tumors. The necessitates multiple biopsies, particularly TC, accurate evaluation. These findings underscore need personalized strategies MIBC, considering increased risk relapse Implementing multi-biopsy approach is critical enhance diagnostic accuracy.
Language: Английский
Citations
0