Annals of Oncology, Journal Year: 2025, Volume and Issue: 36(3), P. 244 - 246
Published: Feb. 19, 2025
Language: Английский
New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 389(23), P. 2162 - 2174
Published: Dec. 6, 2023
Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in United States.We conducted phase 3, global, confirmatory, open-label, randomized, controlled trial to compare efficacy and safety MIRV with investigator's choice chemotherapy platinum-resistant, high-grade serous cancer. Participants who had previously received one three lines therapy high FRα tumor expression (≥75% cells ≥2+ staining intensity) were randomly assigned 1:1 ratio receive (6 mg per kilogram adjusted ideal body weight every 3 weeks) or (paclitaxel, pegylated liposomal doxorubicin, topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic points included objective response, overall survival, participant-reported outcomes.A total 453 participants underwent randomization; 227 group 226 group. median survival 5.62 months (95% confidence interval [CI], 4.34 5.95) 3.98 CI, 2.86 4.47) (P<0.001). An response occurred 42.3% 15.9% those (odds ratio, 3.81; 95% 2.44 5.94; P<0.001). Overall significantly longer than (median, 16.46 vs. 12.75 months; hazard death, 0.67; 0.50 0.89; P = 0.005). During period, fewer adverse events grade higher (41.7% 54.1%), as did serious any (23.9% 32.9%) leading discontinuation (9.2% 15.9%).Among FRα-positive cancer, showed significant benefit over respect response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).
Language: Английский
Citations
130
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: March 28, 2024
Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance bottleneck in ovarian treatment. The increasing use novel drugs clinical practice poses challenges for treatment drug-resistant cancer. Continuing to classify drug according type without understanding underlying mechanisms unsuitable current practice. We reviewed literature regarding various and found that main are as follows: abnormalities transmembrane transport, alterations DNA damage repair, dysregulation cancer-associated signaling pathways, epigenetic modifications. methylation, histone modifications noncoding RNA activity, three key classes modifications, constitute pivotal resistance. One can have multiple mechanisms. Moreover, common chemotherapies targeted may cross (overlapping) MicroRNAs (miRNAs) interfere with thus regulate abovementioned pathways. A subclass miRNAs, “epi-miRNAs”, modulate regulators impact therapeutic responses. Thus, we also regulatory influence miRNAs on summarized recent phase I/II trials based multitude new therapies under evaluation, preliminary results encouraging. This review provides insight into classification facilitate successful resistant
Language: Английский
Citations
54
Taiwanese Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: 63(1), P. 10 - 16
Published: Jan. 1, 2024
In the Part I, we have discussed background of CA125 and development anti-CA125 monoclonal antibody (MAb) to highlight potential role MAb in management women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or O-link is supposed play a modification immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like OV197-like often used for diagnosing, screening, monitoring detecting mesothelin-related diseases abdominal cavity, particular those EOC. Additionally, also plays therapeutic role, named OvaRex MAb-B43.13 (oregovomab), has been extensively reviewed I review article. The main mechanisms include (a) forming immune complexes activate antigen-presenting cells; (b) triggering induction CA125-specific responses, including Abs against various epitopes B T cell responses; (c) CD4 CD8 T-cell responses specific B43.13 produce non-specific response. With success vitro, vivo primitive studies, phase II study was conducted test effectiveness chemoimmunotherapy (CIT) EOC patients. 97 patients after optimal debulking surgery (residual tumor <1 cm no gross residual tumor), treated CIT had dramatical statistically significant improvement both progression-free survival (PFS) overall (OS) compared chemotherapy alone median PFS 41.8 months versus 12.2 (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.28–0.7) OS not yet reached (NE) 42.3 (HR 0.35, CI 0.16–0.74), respectively. current will explore possibility using front-line therapy advanced-stage maximal cytoreductive based on evidence many 2 studies.
Language: Английский
Citations
24
Taiwanese Journal of Obstetrics and Gynecology, Journal Year: 2023, Volume and Issue: 62(6), P. 802 - 808
Published: Nov. 1, 2023
The current standard therapy of epithelial ovarian cancer (EOC) is the combination surgery (primary cytoreductive or interval surgery) and platinum-based chemotherapy (mainly using paclitaxel carboplatin either by neoadjuvant and/or postoperative adjuvant chemotherapy) with/without adding targeted anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, advanced-stage EOC can be successfully controlled three-quarters patients achieve a complete clinical remission. Unfortunately, nearly all will recur progression-free survival (PFS) these seldom more than 3 years with dismal median PFS 12–18 months. With each recurrence, finally develop resistance to regimen, contributing fewer half women who survive for 5 after diagnosis overall (OS) 40.7 Due lower OS, particularly those patients, novel therapeutic options during are desperately needed decrease occurrence majority them still under investigation. It well-known that overexpression CA125 has been associated attenuated cellular apoptosis, platinum resistance, tumor proliferation disease progression, suggesting anti-CA125 may play role in management EOC. review Part I which focus on development monoclonal antibody, hoping alternation chemo-immunotherapy beneficial prolonged
Language: Английский
Citations
29
Science Bulletin, Journal Year: 2024, Volume and Issue: 69(13), P. 2122 - 2135
Published: May 18, 2024
Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various types. Despite extensive efforts, absence a druggable active site small molecules has rendered these mutants therapeutically non-actionable. Here we develop selective effective proteolysis-targeting chimera (PROTAC) p53-R175H, common hotspot with dominant-negative activity. Using novel iterative molecular docking-guided post-SELEX (systematic evolution ligands by exponential enrichment) approach, rationally engineer high-performance DNA aptamer improved affinity specificity p53-R175H. Leveraging this resulting as binder PROTACs, successfully developed p53-R175H degrader, named dp53m. dp53m induces ubiquitin-proteasome-dependent degradation while sparing wildtype p53. Importantly, demonstrates significant antitumor efficacy p53-R175H-driven cells both vitro vivo, without toxicity. Moreover, significantly synergistically improves sensitivity cisplatin, commonly used chemotherapy drug. These findings provide evidence potential therapeutic value cancers.
Language: Английский
Citations
13
Biomolecules, Journal Year: 2024, Volume and Issue: 14(5), P. 585 - 585
Published: May 15, 2024
Epithelial ovarian cancer (EOC) is one of the most aggressive forms gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as patients are advanced disease. Debulking surgery and platinum-based therapies current mainstay treatment. However, despite achieving initial remission, a significant portion will relapse because innate acquired resistance, at which point disease considered incurable. In view this, novel detection strategies therapeutic approaches needed to improve outcomes survival patients. this review, we summarize our knowledge genetic landscape molecular pathways underpinning its many subtypes. By examining explored in preclinical clinical settings, highlight importance decoding how single convergent alterations co-exist drive progression resistance treatments. We also propose that core signalling such PI3K MAPK play critical roles origin diverse subtypes can become new targets combination known DNA damage repair development tailored more effective anti-cancer
Language: Английский
Citations
9
Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 23, 2025
Abstract Abnormal expression of transmembrane mucin 16 (MUC16) in ovarian cancer (OC) can promote progression epithelial–mesenchymal transformation, enhance tumor cell proliferation, migration, and invasion. Therefore, herein a targeted therapeutic high‐valence selenium (Se) nanomedicine (MUC16‐SeMnf@Res) is designed, which target MUC16 to recognize OC simultaneously inhibit achieve efficient treatment OC. The valence bidirectional editing strategy used design synthesize Se nanosystem (SeMnf) through triggering redox reaction between triclinic manganese dioxide nanoflower (Mnf), inducing the conversion 4+ Mn 2+ . increased ratio within SeMnf disrupt intracellular homeostasis by glutathione (GSH) depletion reactive oxygen species (ROS) overproduction. Moreover, effects ROS overproduction are further amplified loaded resveratrol (Res), significantly induces mitochondrial dysfunction inhibited expression, then promoting caspase‐activated apoptosis as well migration inhibitory. Taken together, this study not only sheds light on important role designing OC‐targeting drugs, but also provides simple translational developing nanotherapeutics with strong redox‐homeostasis disrupting capability realize MUC16‐targeting therapy.
Language: Английский
Citations
1
Immunology, Journal Year: 2024, Volume and Issue: 173(1), P. 14 - 32
Published: April 15, 2024
Despite progress in cancer immunotherapy, ovarian (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex microenvironment, contribute this unfavourable outcome of OC immunotherapy. The complexities immune microenvironment categorize as a 'cold tumour'. Nonetheless, understanding precise mechanisms through which influences effectiveness immunotherapy remains an ongoing scientific endeavour. This review primarily aims dissect inherent characteristics and behaviours diverse cells within along with exploration into its reprogramming metabolic changes. It is expected that these insights will elucidate operational dynamics lay theoretical groundwork for improving efficacy management.
Language: Английский
Citations
7
Expert Opinion on Investigational Drugs, Journal Year: 2024, Volume and Issue: 33(6), P. 639 - 651
Published: April 27, 2024
FAK, a nonreceptor cytoplasmic tyrosine kinase, plays crucial role in tumor metastasis, drug resistance, stem cell maintenance, and regulation of the microenvironment. FAK has emerged as promising target for therapy based on both preclinical clinical data.
Language: Английский
Citations
6
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116736 - 116736
Published: May 12, 2024
The xanthone dimer 12-O-deacetyl-phomoxanthone A (12-ODPXA) was extracted from the secondary metabolites of endophytic fungus Diaporthe goulteri. 12-ODPXA compound exhibited anticancer properties in murine lymphoma; however, anti-ovarian cancer (OC) mechanism has not yet been explored. Therefore, present study evaluated whether reduces OC cell proliferation, metastasis, and invasion by downregulating pyruvate dehydrogenase kinase (PDK)4 expression.
Language: Английский
Citations
6