A5023027543- Glutathione Transferases and Polymorphisms
- Bioactive Compounds and Antitumor Agents
- Cell death mechanisms and regulation
- Cancer Treatment and Pharmacology
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- Advanced Breast Cancer Therapies
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Tannin, Tannase and Anticancer Activities
- Peptidase Inhibition and Analysis
- Synthesis and biological activity
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cancer Mechanisms and Therapy
- Mechanisms of cancer metastasis
- Nuclear Receptors and Signaling
- Brain Metastases and Treatment
- Kruppel-like factors research
- Virus-based gene therapy research
- Computational Drug Discovery Methods
- Nanoplatforms for cancer theranostics
- Synthesis and Characterization of Heterocyclic Compounds
University of California, San Diego
2016-2025
UC San Diego Health System
2017-2024
University College London
2024
Moores Cancer Center
2015-2024
Roland Hill (United Kingdom)
2024
Institute of Infection and Immunity
2024
Entertainment Industry Foundation
2009-2023
New York University
2009-2023
AstraZeneca (United Kingdom)
2015
Cornell University
2004
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management breast cancer. treatment landscape metastatic cancer is evolving constantly. therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number options, if one option fails, there usually another line therapy available, providing meaningful improvements survival. This Insights report focuses on recent updates...
Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer include recommendations clinical management of patients carcinoma situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory during pregnancy. content featured this issue focuses on the overall systemic therapy (preoperative adjuvant) options nonmetastatic cancer. For full...
Abstract Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have revolutionized breast cancer therapy. However, <50% of patients an objective response, nearly all develop resistance during To elucidate the underlying mechanisms, we constructed interpretable deep learning model response to palbociclib, a CDK4/6i, based on reference map multiprotein assemblies in cancer. The identifies eight core that integrate rare common alterations across 90 genes stratify palbociclib-sensitive versus...
The RAS/RAF/MEK/ERK signaling pathway has been targeted with a number of small molecule inhibitors in oncology clinical development across multiple disease indications. Importantly, cell lines acquired resistance to B-RAF and MEK have shown maintain sensitivity ERK1/2 inhibition by inhibitors. There are selective, noncovalent reported along the promiscuous hypothemycin (and related analogues) that act via covalent mechanism action. This article reports identification series highly selective...
Abstract Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fueled by tumor cell's ability to “secrete-and-sense” factors (GFs); this translates into cell survival and proliferation that self-sustained autocrine/paracrine secretion. A Golgi-localized circuitry comprised two GTPase switches has recently been implicated orchestration signaling autonomy. Using breast cancer cells are either endowed or impaired (by gene editing) their assemble for...
We previously reported that expression of NRIF3 (nuclear receptor interacting factor-3) rapidly and selectively leads to apoptosis breast cancer cells. DIF-1 (also known as interferon regulatory factor-2 binding protein 2 [IRF-2BP2]), the cellular target NRIF3, was identified a transcriptional repressor, knockdown cells but not other cell types. Here, we identify IRF-2BP1 EAP1 (enhanced at puberty 1) important components complex mediating both stability repression. This interaction DIF-1,...
Abstract The rapid evolution of machine learning has led to a proliferation sophisticated models for predicting therapeutic responses in cancer. While many these show promise research, standards clinical evaluation and adoption are lacking. Here, we propose seven hallmarks by which predictive oncology can be assessed compared. These Data Relevance Actionability, Expressive Architecture, Standardized Benchmarking, Generalizability, Interpretability, Accessibility Reproducibility, Fairness....
Recent studies suggest a functional involvement of Epithelial-Mesenchymal Transition (EMT) in tumor chemoresistance. Specifically, EMT is associated with chemoresistance and poor prognosis triple-negative breast cancer. However, no effective therapy targeting has been developed. Here, we report that periostin, an extracellular matrix protein, was induced upon chemotherapy tightly correlated the gene signature In cancer xenografts, upregulated periostin expression cells, triggered expansion...
Abstract Expression of the nuclear receptor interacting factor 3 (NRIF3) coregulator in a wide variety breast cancer cells selectively leads to rapid caspase-2–dependent apoptotic cell death. A novel death domain (DD1) was mapped 30–amino acid region NRIF3. Because cytotoxicity NRIF3 and DD1 seems be type–specific, these studies suggest that contain “death switch” can specifically modulated by or DD1. Using an MCF-7 cDNA library yeast two-hybrid screen, we cloned mediates apoptosis refer...
Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of that lacks an effective targeted therapy. To identify new therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in development several types cancer. However, full significance LHPP progression remains unclear due to our limited understanding its molecular mechanism. We found levels phosphatase were significantly increased human patients compared normal adjacent...
Abstract Purpose of Review Triple-negative breast cancer (TNBC) is a heterogeneous disease group with known aggressive phenotype and poor prognosis. To date, it remains challenging given its lack oncogenic targets as seen in hormone receptor + or HER2 cancers, limited efficacy traditional chemotherapy. This article review the latest key literature management metastatic TNBC offers glimpse ongoing drug development. Recent Findings paradigm-shifting trials led to incorporation immune...
Expression of NRIF3 (Nuclear Receptor Interacting Factor-3) rapidly and selectively leads to apoptosis breast cancer cells. This occurs through binding or its 30 amino acid Death Domain-1 (DD1) region the transcriptional repressor, DIF-1 (DD1 Factor-1). acts in a wide variety cells but not other cell types repress pro-apoptotic gene, FASTKD2. DD1 inactivates repressor leading rapid derepression FASTKD2, which initiates within 5–8 h expression. Although FASTKD2 is an inner mitochondrial...
e13117 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that revolutionized the management of patients with HER2+ (HER2 FISH+, IHC 3+) and HER2 low FISH-, 1+/2+) metastatic breast cancer (MBC). Studies have shown T-DXd may induce antitumor activity in MBC brain metastases (BM). However, data limited on central nervous system (CNS) efficacy disease. The only report thus far from cohorts DEBBRAH study 12 showing intracranial overall response rate (ORR-IC) 50%...
LBA520 Background: I-SPY 2 is a multicenter trial using response-adaptive randomization within biomarker subtypes including MammaPrint (MP) risk to evaluate novel neoadjuvant agents in high-risk breast cancer. Oral paclitaxel and encequidar (OPE) an oral combination of (P) with p-glycoprotein pump inhibitor, encequidar, enhance gastrointestinal (GI) absorption. Dostarlimab (D) anti-PD-1 monoclonal antibody. Methods: Women tumors ≥ 2.5cm MP cancers were screened treated starting Oct 5, 2020....
Abstract Background: HER2-targeted therapies have led to marked improvements in survival for patients with HER2-positive breast cancer. Despite the gains obtained current therapies, an unmet medical need remains HER2-expressing (high or low expression) advanced cancer that has progressed after prior treatments. Zanidatamab is a novel bispecific antibody multiple mechanisms of action, including immune clearance tumor cells through antibody-dependent cellular phagocytosis. been shown be...
The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens andare key targets in cancer immunotherapy. Both pathways are connected via a cisinteraction between CD80 PD-L1, the ligands for respectively.This cis interaction prevents binding PD-L1 but is reversed by transendocytosisof CD80. However, mechanism which selectively removesCD80 not unclear. Here we show that – interactions areunimpeded with does displace PD-L1per se. Rather, both rigidity bivalency of WT molecule...
Abstract The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens are key targets in cancer immunotherapy. Both pathways connected via a cis interaction between CD80 PD-L1, the ligands for respectively. This prevents binding PD-L1 but is reversed by trans-endocytosis of CD80. However, mechanism which selectively removes not unclear. Here we show that – interactions unimpeded with does displace per se. Rather, both rigidity bivalency WT molecule required orientate such no...