A5016505594- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Nanoparticle-Based Drug Delivery
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Metabolism, Diabetes, and Cancer
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Angiogenesis and VEGF in Cancer
- Cancer Genomics and Diagnostics
- Nanoplatforms for cancer theranostics
- Growth Hormone and Insulin-like Growth Factors
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Renal cell carcinoma treatment
- Nuclear Receptors and Signaling
- Endometrial and Cervical Cancer Treatments
- Chromatin Remodeling and Cancer
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Acute Myeloid Leukemia Research
Mayo Clinic in Arizona
2016-2025
Mayo Clinic
2016-2025
WinnMed
2018-2024
Cleveland Clinic
2024
Mayo Clinic in Florida
2019-2023
Bristol-Myers Squibb (United States)
2010
Immunovaccine (Canada)
2009
Abstract ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis pre- and post-platinum samples, RAD51C RAD51D mutations high-level BRCA1 promoter methylation predict response to rucaparib, similar / BRCA2 mutations. loss may be major cross-resistance mechanism platinum PARPi. Genomic scars associated with homologous recombination deficiency are...
Replication stress and DNA damage activate the ATR-Chk1 checkpoint signaling pathway that licenses repair cell survival processes. In this study, we examined respective roles of ATR Chk1 kinases in ovarian cancer cells using genetic pharmacologic inhibitors combination with cisplatin, topotecan, gemcitabine, PARP inhibitor veliparib (ABT-888), four agents clinical activity cancer. RNA interference (RNAi)-mediated depletion or inhibition sensitized to all agents. contrast, while gemcitabine...
In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was predictive biomarker. Only high-risk disease (suboptimally resected stage III, or IV) exhibiting KELIM score < 1.0 had overall survival (OS) benefit from (median: 29.7
1011 Background: Chemotherapy is a standard of care for TNBC despite its suboptimal efficacy. ≈15–20% have BRCA1/2 mutations (mut); ≈75% BRCA1 mut BCs are TN. Single agent poly(ADP-ribose) polymerase (PARP) inhibitors clinical activity in pts with (BRCAmut) BC and provide median PFS 6 mos BRCAmut vs 3.5 chemotherapy. Single-agent pembrolizumab (pembro), programmed death 1(PD–1) inhibitor, has shown objective response rates (ORR) 5–18% previously treated TNBC. TOPACIO (NCT02657889) fully...
Abstract In a trial of patients with high grade serous ovarian cancer (HGSOC), addition the ATR inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared alone but biomarkers predictive treatment are lacking. Here we report candidate biomarker response versus combined and therapy in HGSOC cancer. Patients replication stress (RS)-high tumors (n = 27), defined as harboring at least one genomic RS alteration related loss RB pathway regulation and/or oncogene-induced...
BRCA1 plays a key role in homologous recombination (HR) DNA repair. Accordingly, changes that downregulate BRCA1, including mutations and reduced transcription, due to promoter hypermethylation or loss of the transcriptional regulator CDK12, disrupt HR multiple cancers. In addition, has also been implicated regulation metabolism. Here, we show reducing expression, either by CDK12 depletion, led metabolic reprogramming ovarian cancer cells, causing decreased mitochondrial respiration ATP...
Abstract Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated (MTD), and recommended phase II (RP2D) of veliparib in combination with weekly topotecan patients solid tumors. Correlative studies were included to assess impact on poly(ADP-ribose) levels peripheral blood mononuclear cells, serum pharmacokinetics both agents, potential association germline repair gene mutations outcome. Experimental Design: Eligible had metastatic nonhematologic malignancies measurable...
AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels VEGF. Preclinical data showed that resulted in greater tumor targeting and inhibition compared sequential treatment ABX then BEV. Given individual drug activity, we investigated the safety toxicity patients gynecologic cancers.
Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib evaluated in combination with determine the maximum tolerated dose (MTD) and limiting toxicities (DLT). In this single arm multicohort phase I trial, we safety efficacy plus patients advanced solid tumors. Patients received intravenously days 1 8 followed by 8–14, treatment repeated every 3 weeks. The study enrolled 43 between October 2017 September 2019. escalation (19 patients)...
Objectives: Abemaciclib, a selective inhibitor of cyclin-dependent kinase 4 and 6, olaparib, poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, are used for cancer treatment. Early toxicity was observed in patients with recurrent platinum-resistant ovarian an ongoing trial evaluating combined abemaciclib olaparib (NCT04633239). Since metabolism transport pathways partially overlap, since cycle 1 pharmacokinetic (PK) data suggested drug-drug interactions (DDI) this patient population, we...
Acquired PARP inhibitor (PARPi) resistance in BRCA1- or BRCA2-mutant ovarian cancer often results from secondary mutations that restore expression of functional protein. RAD51C is a less commonly studied susceptibility gene whose promoter sometimes methylated, leading to homologous recombination (HR) deficiency and PARPi sensitivity. For this study, the PARPi-sensitive patient-derived xenograft PH039, which lacks HR but harbors methylation, was selected for by cyclical niraparib treatment...
The insulin receptor (IR) and insulin-like growth factor-1 (IGF1R) are tyrosine kinases that participate in mitogenic antiapoptotic signaling normal neoplastic epithelia. In the present study, immunoblotting reverse transcription-PCR demonstrated expression of IGF1R IR isoform A acute myelogenous leukemia (AML) cell lines as well >80% clinical AML isolates. Treatment with enhanced through Akt MEK1/2 pathways survival serum-starved lines. Conversely, treatment BMS-536924, a dual IGF1R/IR...
PURPOSE The multicenter, open-label, randomized phase 2 NCI-9944 study ( NCT02595892 ) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the significance level 0.1 used for sample size calculation). METHODS We report here final overall (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 a...
5557 Background: Deregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6) – p16 Rb signaling pathway is commonly found in ovarian cancer (OC). Palbociclib an inhibitor CDK4/6 was recently shown to delay disease progression postmenopausal women with advanced breast cancer. Here we study safety efficacy palbociclib patients (pts) recurrent OC. Methods: Asymptomaticpts RECIST and/or CA125 measurable failing chemotherapy or anti-hormonal therapy were given oral 125 mg once daily for 3 weeks...