Ningping Feng
A5071445059- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Ovarian cancer diagnosis and treatment
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Glioma Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Protein Tyrosine Phosphatases
- Inflammatory mediators and NSAID effects
- DNA Repair Mechanisms
- Acute Myeloid Leukemia Research
- Mitochondrial Function and Pathology
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- Toxin Mechanisms and Immunotoxins
- Cancer Mechanisms and Therapy
The University of Texas MD Anderson Cancer Center
2016-2025
Shanxi Agricultural University
2025
National Institute of Mental Health
2014-2023
United States Department of Health and Human Services
2021
National Institute of Mental Health
2019
National Institutes of Health
2003-2018
Johns Hopkins Medicine
2009
Johns Hopkins University
2009
Arius3D (Canada)
2007-2008
In-Q-Tel
2007
Abstract PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and breast cancers with germline mutation. However, resistance to may preexist or evolve during treatment many types be overcome by combining other therapies, such as immune checkpoint inhibitors, which confer durable responses are rapidly becoming the standard care for multiple tumor types. This study investigated therapeutic potential niraparib, a highly...
Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways overcome resistance, an urgent clinical need all relapsed/refractory cancers, remains difficult. Through genomic analyses specimens, we show that toward oxidative phosphorylation (OXPHOS) glutaminolysis associated with the Bruton's tyrosine kinase inhibitor ibrutinib mantle lymphoma (MCL), B subtype poor outcomes....
KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated adagrasib or sotorasib, mutations PIK3CA and KRAS, amplifications of KRASG12C, MYC, MET, EGFR, CDK6 emerged at acquired resistance. In cell lines organoid models the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition PI3K-AKT-mTOR signaling associate to therapy. MRTX1133 treatment KrasLSL-G12D/+;...
Abstract Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation disease progression. Therefore, the development agents that overcome dysregulation in tumor cells is an attractive therapeutic approach. Activation extrinsic apoptotic pathway strongly dependent on receptor (DR) hyperclustering surface. However, strategies activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue alternative approach for...
Though the efficacy of MEK inhibitors is being investigated in KRAS-mutant colorectal cancers (CRC), early clinical trials inhibitor monotherapy did not reveal significant antitumor activity. Resistance to developed through a variety mechanisms converging ERK reactivation. Since increases cyclin D expression and entry into cell cycle, we hypothesized that combination CDK4/6 would have synergistic activity cause tumor regression vivo.The synergistically inhibited cancer growth vitro caused...
Src homology 2 domain-containing phosphatase (SHP2) is a that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and required for full activation the MAPK pathway. SHP2 inhibition has demonstrated tumor growth in RTK-activated cancers preclinical studies. The long-term effectiveness kinase inhibitors such as EGFR inhibitor (EGFRi), osimertinib, non-small cell lung cancer (NSCLC) limited by acquired resistance. Multiple clinically identified mechanisms underlie...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for cell survival and demonstrate direct relationship between , elevated OxPhos gene expression, acquired chemoresistance pre-leukemic leukemic models. Disrupting with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction...
Abstract Combination approaches are needed to strengthen and extend the clinical response KRAS G12C inhibitors (KRAS i). Here, we assessed antitumor responses of mutant lung colorectal cancer models combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus inhibitor, adagrasib. We found that BI-3406 adagrasib were stronger than alone, comparable SHP2 (SHP2i) or EGFR correlated suppression RAS-MAPK signaling. also delayed emergence acquired resistance elicited from...
The purpose of this study is to determine if inhibition mitochondrial oxidative phosphorylation (OxPhos) an effective strategy against MAPK pathway inhibitor (MAPKi)-resistant BRAF-mutant melanomas.Experimental Design: antimelanoma activity IACS-010759 (OPi), a novel OxPhos complex I inhibitor, was evaluated in vitro and vivo. Mechanistic studies predictors response were using molecularly metabolically stratified melanoma cell lines. 13C-labeling targeted metabolomics used evaluate the...
Inhibition of glutaminase-1 (GLS-1) hampers the proliferation tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused optimizing pharmacokinetic properties, developed new selective inhibitor, compound 27 (IPN60090), which is currently phase 1 clinical trials. Compound attains high oral preclinical species, with...
The plasticity of a preexisting regulatory circuit compromises the effectiveness targeted therapies, and leveraging genetic vulnerabilities in cancer cells may overcome such adaptations. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is characterized by oxidative phosphorylation (OXPHOS) deficiency caused fumarate hydratase (FH) nullizyogosity. To identify metabolic genes that are synthetically lethal with OXPHOS deficiency, we conducted loss-of-function screen found phosphogluconate...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ RNAi-based in vivo functional genomics platform determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, identify protein arginine methyltransferase 1 (PRMT1) as critical dependency required for maintenance. Genetic and pharmacological studies validate the role PRMT1 maintaining growth. Mechanistically, using proteomic...
On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with AKT inhibitor capivasertib and assess molecular markers response resistance.We performed safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily on 4-day 3-day off schedule was evaluated. Two levels (DL) were planned: 400 (DL1) 320 (DL-1)....
Abstract Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions mitochondrial to tumor growth therapy resistance evident, but drugs targeting have repeatedly failed in the clinic. Our study pancreatic ductal adenocarcinoma (PDAC) finds that cellular lipid composition influence cancer cell sensitivity pharmacological inhibition electron transport chain complex I. Profiling...
Both human linkage studies and MC3R knockout mouse models suggest that the may play an important role in energy homeostasis. Here we show among 355 overweight nonoverweight children, 8.2% were double homozygous for a pair of missense sequence variants (Thr6Lys Val81Ile). Such children significantly heavier (BMI BMI SD score: P < 0.0001), had more body fat (body mass percentage mass: 0.001), greater plasma leptin (P 0.0001) insulin concentrations 0.001) resistance 0.008) than wild-type...
Abstract A 4 kb human interleukin‐13 receptor (IL‐13R) chain cDNA was cloned from a B cell library using expressed sequence tags homologous to mouse IL‐13R as probes. The deduced protein shows significant level of identity with the IL‐5R and identified recently by expression cloning. cytoplasmic region is very highly conserved between homologs contains consensus binding motif for signal transducer activator transcription. encodes IL‐13 when alone which participates in complex both IL‐4...