Cancer Discovery, Год журнала: 2024, Номер 14(11), С. 2089 - 2108
Опубликована: Окт. 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.
Язык: Английский
Процитировано
23Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing
Current Oncology Reports, Год журнала: 2025, Номер unknown
Опубликована: Янв. 5, 2025
Язык: Английский
Процитировано
1Five-gene expression signature associated with acquired FOLFIRI resistance and survival in metastatic colorectal cancer.
Laboratory Investigation, Год журнала: 2025, Номер unknown, С. 104107 - 104107
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0Antibody–Drug Conjugates in Non-Small Cell Lung Cancer: State of the Art and Future Perspectives
International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 221 - 221
Опубликована: Дек. 30, 2024
Antibody–drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine cytotoxic effect conjugate payload high selectivity monoclonal antibody, which binds a specific membrane antigen expressed by tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (HER2), 3 (HER3), trophoblast surface (TROP2), Mesenchymal–epithelial transition (c-MET), carcinoembryonic antigen-related adhesion molecule 5 (CEACAM5). To date, Trastuzumab deruxtecan is only ADC that has been approved FDA for treatment patients with NSCLC, but several ongoing studies, both using as monotherapy combined other therapies, investigating efficacy new ADCs. this review, we describe structures mechanism action different ADCs; present evidence derived from main clinical trials ADCs’ efficacy, focusing also on related toxicity; and, finally, discuss future perspectives in terms toxicity management, possible biomarkers, identification resistance mechanisms.
Язык: Английский
Процитировано
3Antibody-drug conjugates in NSCLC with actionable genomic alterations: Optimizing smart delivery of chemotherapy to the target
Cancer Treatment Reviews, Год журнала: 2025, Номер 134, С. 102902 - 102902
Опубликована: Фев. 16, 2025
Язык: Английский
Процитировано
0Polysaccharides as therapeutic vehicles in pancreatic cancer
Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104320 - 104320
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0Expanding the potential of antibody–drug conjugates in gastrointestinal malignancies: beyond HER2 targets
ESMO Gastrointestinal Oncology, Год журнала: 2025, Номер 8, С. 100154 - 100154
Опубликована: Март 19, 2025
Язык: Английский
Процитировано
0The Role of Genomics and Transcriptomics in Characterizing and Predicting Patient Response to Treatment in Triple Negative Breast Cancer (TNBC)
Onco, Год журнала: 2025, Номер 5(2), С. 18 - 18
Опубликована: Апрель 22, 2025
Breast cancer is a complex disease that one of the leading causes cancer-related mortality in women worldwide. Of subtypes breast cancer, most aggressive subtype triple negative (TNBC) due to its lack targets could be leveraged for treatment other subtypes. Current options both local and metastatic TNBC include radiation therapy, chemotherapy, surgery, targeted immunotherapy, which has been gaining popularity recent years. The role therapy somewhat limited paucity therapeutic personalized targets, and, heterogeneity disease, effectiveness these different modalities varies from patient patient. These unique elements are foundation medicine where genomics transcriptomics play critical increasing granularity patients’ treatment. purpose molecular tools identify biomarkers used further characterize each patient’s features predict how certain will affect survival prognosis. interplay between pathways involved response with progression aggressiveness phenomenon. In this review, we describe current state literature regard show promise clinical setting treatments such as radiation, surgery locally advanced TNBC.
Язык: Английский
Процитировано
0Decoding Clinical Trials in Metastatic Breast Cancer: Practical Insights for Optimal Therapy Sequencing
American Society of Clinical Oncology Educational Book, Год журнала: 2025, Номер 45(3)
Опубликована: Май 14, 2025
The art of sequencing therapy in the management breast cancer is a multifaceted challenge that demands careful integration clinical trial data, real-world evidence, and individualized patient factors to guide treatment decisions. As therapeutic landscape evolves rapidly with new agents combinations, clinicians are confronted critical decisions on how best order treatments maximize benefit, minimize toxicity, preserve future options. For patients estrogen receptor–positive (ER+) disease, this review discusses emerging resistance patterns after cyclin-dependent kinase 4 6 inhibitors require re-evaluation subsequent endocrine targeted therapies, as well chemotherapy, emphasizing need for evidence-based strategies ethical crossover designs trials. In addition, both ER+ ER– metastatic (MBC) nonoverexpressed human epidermal growth factor receptor 2 (HER2), highlights pivotal trials investigating antibody-drug conjugates (ADCs)—including trastuzumab deruxtecan, sacituzumab govitecan, datopotamab deruxtecan—and challenges related control arm selection may affect outcome interpretation. Finally, HER2-positive explores first-line maintenance strategies—including insights from landmark like CLEOPATRA PATINA—and addresses impact brain metastases By critically appraising current data identifying gaps biomarker-guided sequencing-specific strategies, provides practical inform practice optimize personalized plans MBC.
Язык: Английский
Процитировано
0Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas
Cancer Chemotherapy and Pharmacology, Год журнала: 2025, Номер 95(1)
Опубликована: Май 29, 2025
Abstract Purpose Indenoisoquinolines are a class of topoisomerase I (TOP1) inhibitors designed to overcome clinical limitations camptothecins. Three indenoisoquinolines (LMP400, LMP776, and LMP744) demonstrated activity in murine models comparative canine lymphoma study. Clinical data for LMP400 were previously reported (NCT01051635). The maximum tolerated dose (MTD), safety, from phase 1 studies LMP776 (NCT01051635) LMP744 (NCT03030417) herein. Methods Patients ≥ 18 years age with advanced, refractory solid tumors or lymphomas received either (n = 34) 35) intravenously following Simon accelerated titration design. Both administered daily 5 days (QDx5) 28-day cycles. Adverse events responses evaluated according CTCAE RECIST v1.1 criteria, respectively. Pharmacokinetic pharmacodynamic changes evaluated. Results MTD was 12 mg/m 2 /day that 190 /day. Dose-limiting toxicities (DLTs) included hypercalcemia, anemia, hyponatremia; DLTs hypokalemia, weight loss. There confirmed partial response (cPR) among 35 patients receiving (overall rate 3%) no objective LMP776. Tumor biopsies the patient cPR high baseline expression SLFN11 unique pattern responses, including increased RAD51, phosphorylated KAP1 (pKAP1), γH2AX, cleaved caspase-3 (cCasp3). Conclusion MTDs safety profiles LMP744. Target engagement by an indenoisoquinoline measured first time human samples.
Язык: Английский
Процитировано
0