Modern Pathology, Год журнала: 2025, Номер unknown, С. 100752 - 100752
Опубликована: Март 1, 2025
Язык: Английский
Cells, Год журнала: 2022, Номер 11(23), С. 3835 - 3835
Опубликована: Ноя. 29, 2022
cAMP-dependent pathway is one of the most significant signaling cascades in healthy and neoplastic ovarian cells. Working through its major effector proteins—PKA EPAC—it regulates gene expression many cellular functions. PKA promotes phosphorylation cAMP response element-binding protein (CREB) which mediates transcription, cell migration, mitochondrial homeostasis, proliferation, death. EPAC, on other hand, involved adhesion, binding, differentiation, interaction between junctions. Ovarian cancer growth metabolism largely depend changes signal processing cAMP-PKA-CREB axis, often associated with transformation, metastasis, inhibition apoptosis. In addition, intracellular level also determines course pathways including AKT, ERK, MAPK, mTOR, that are hypo- or hyperactivated among patients neoplasm. With this review, we summarize current findings ovary association carcinogenesis, multiplication, survival Additionally, indicate targeting particular stages processes might provide promising therapeutic opportunities for effective management cancer.
Язык: Английский
Процитировано
28
Journal of Gynecologic Oncology, Год журнала: 2024, Номер 35(3)
Опубликована: Янв. 1, 2024
Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors maintenance therapy have markedly improved outcomes patients with specific genetic profiles, such as those positive BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, method intraperitoneal administration emerged a valuable alternative to traditional transvenous routes, showing promise wider clinical adoption. The field surgery also evolved, increasing exploration into benefits feasibility laparoscopic methods over more invasive surgeries, aiming complete tumor removal but reduced patient impact. hereditary nature ovarian cancer underscores importance testing, which become integral tailoring strategies, particularly determining suitability PARP inhibitors. formation East Asian Gynecologic Oncology Trial Group (EAGOT) aims optimize across Japan, Korea, China, Taiwan. committee EAGOT shared current policies, focusing on 5 topics: 1) strategies after initial chemotherapy, 2) drug regimens platinum-sensitive platinum-resistant recurrence, 3) 4) an laparotomy, 5) status testing (BRCA, HRD, panel tests) prospects. EAGOT's multi-national trials aim harmonize these evolving ensuring that latest most effective are accessible region, thereby significantly impacting Asia.
Язык: Английский
Процитировано
6
Cells, Год журнала: 2024, Номер 13(13), С. 1083 - 1083
Опубликована: Июнь 22, 2024
Regulated cell death, a regulatory form of demise, has been extensively studied in multicellular organisms. It plays pivotal role maintaining organismal homeostasis under normal and pathological conditions. Although alterations various regulated death modes are hallmark features tumorigenesis, they can have divergent effects on cancer cells. Consequently, there is growing interest targeting these mechanisms using small-molecule compounds for therapeutic purposes, with substantial progress observed across human cancers. This review focuses summarizing key signaling pathways associated apoptotic autophagy-dependent death. Additionally, it explores crucial related to other the context cancer. The discussion delves into current understanding processes their implications treatment, aiming illuminate novel strategies combat therapy resistance enhance overall therapy.
Язык: Английский
Процитировано
6
Cancer Research, Год журнала: 2024, Номер 84(20), С. 3419 - 3434
Опубликована: Авг. 26, 2024
Abstract Defects in DNA repair pathways play a pivotal role tumor evolution and resistance to therapy. At the same time, they create vulnerabilities that render tumors dependent on remaining processes. This phenomenon is exemplified by clinical activity of PARP inhibitors with homologous recombination (HR) defects, such as inactivating mutations BRCA1 or BRCA2. However, development BRCA-mutant represents high unmet need. In this study, we identified deubiquitinase ubiquitin-specific peptidase-1 (USP1) critical dependency BRCA other forms HR deficiency developed KSQ-4279, first potent selective USP1 inhibitor enter testing. The combination KSQ-4279 was well tolerated induced durable regression across several patient-derived PARP-resistant models. These findings indicate represent promising therapeutic strategy for overcoming patients BRCA-mutant/HR-deficient support continued testing trials. Significance: induces inhibitor–resistant when dosed inhibitors, addressing an need tumors.
Язык: Английский
Процитировано
6
JAMA Oncology, Год журнала: 2024, Номер unknown
Опубликована: Окт. 31, 2024
The prognosis for patients with glioblastoma is poor following standard therapy surgical resection, radiation, temozolomide, and tumor-treating fields.
Язык: Английский
Процитировано
6
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115151 - 115151
Опубликована: Июль 18, 2023
Ovarian cancer is a highly lethal disease that affects women. Early diagnosis and treatment of women with early-stage improve the probability survival. Unfortunately, majority ovarian are diagnosed at advanced stages 3 4 which makes challenging. While patients respond to first-line treatment, i.e. cytoreductive surgery integrated platinum-based chemotherapy, rate recurrence very high available options for recurrent not curative. Thus, there need more effective cancer. Targeted drug conjugate systems have emerged as promising therapeutic strategy These provide opportunity selectively deliver potent chemotherapeutic drugs cancer, sparing healthy normal cells. effectiveness improved systemic toxicity greatly reduced. In this review, different targeted been or being developed will be discussed.
Язык: Английский
Процитировано
14
European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2024, Номер 51(13), С. 4099 - 4110
Опубликована: Июль 18, 2024
Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), significant clinical benefit of SSTR2-targeted radionuclide therapies was not observed so far. We hypothesize that combination treatment PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness therapy in SCLC.
Язык: Английский
Процитировано
5
Chemical Society Reviews, Год журнала: 2024, Номер 53(19), С. 9582 - 9608
Опубликована: Янв. 1, 2024
Targeted protein degradation (TPD) has emerged as a revolutionary paradigm in drug discovery and development, offering promising avenue to tackle challenging therapeutic targets. Unlike traditional approaches that focus on inhibiting function, TPD aims eliminate proteins of interest (POIs) using modular chimeric structures. This is achieved through the utilization proteolysis-targeting chimeras (PROTACs), which redirect POIs E3 ubiquitin ligases, rendering them for by cellular ubiquitin-proteasome system (UPS). Additionally, other technologies such lysosome-targeting (LYTACs) autophagy-based degraders facilitate transportation endo-lysosomal or autophagy-lysosomal pathways degradation, respectively. Despite significant growth preclinical research, many fail progress beyond this stage development. Various factors contribute limited success agents, including hurdle inadequate delivery target site. Integrating into platforms could surmount challenges
Язык: Английский
Процитировано
5
Frontiers in Oncology, Год журнала: 2025, Номер 14
Опубликована: Янв. 16, 2025
Patients with ovarian cancer commonly experience metastases and recurrences, which contribute to high mortality. Our objective was better understand metastasis identify candidate biomarkers drug targets for predicting preventing recurrence. Transcripts of 770 cancer-associated genes were compared in cells collected from ascitic fluid versus resected tumors an ES-2 orthotopic mouse model. Associated cell types pathways explored bioinformatics. FGF7 protein measured using capillary-based immunoassays or ELISA clinical specimens. Significances differential gene expression patient prognosis determined by volcano plot log-rank test, respectively. Tumor transcriptomes exhibited higher endothelial cells, oxygenation, proteasome activity, metabolism comparison ascites, but similar percentages fibroblasts immune cells. mRNA significantly ascites. than ascites independent models Serum levels above the median 25 patients associated worse progression-free overall survival (p = 0.005 0.019, respectively) tumor characteristics. In exhibit different transcriptomic profiles that Among these, elevated tumoral validated at level serum survival. These results support further development receptor-targeted drugs prevent predict recurrence,
Язык: Английский
Процитировано
0
Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104698 - 104698
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0