A5088603617- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Advanced Breast Cancer Therapies
- Neuroendocrine Tumor Research Advances
- Sarcoma Diagnosis and Treatment
- Adrenal and Paraganglionic Tumors
- Renal cell carcinoma treatment
- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Heat shock proteins research
- Neuroblastoma Research and Treatments
- Gastrointestinal Tumor Research and Treatment
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Integrated Circuits and Semiconductor Failure Analysis
- Cancer Treatment and Pharmacology
- RNA modifications and cancer
- Health Systems, Economic Evaluations, Quality of Life
- Cell Image Analysis Techniques
- Immune cells in cancer
AstraZeneca (United States)
2022-2025
Center for Cancer Research
2013-2023
AstraZeneca (Japan)
2023
MacroGenics (United States)
2020-2022
AstraZeneca (United Kingdom)
2022
National Institutes of Health
2011-2020
National Cancer Institute
2011-2019
Molecular Oncology (United States)
2017
Hospital General de Niños Ricardo Gutierrez
2006
Background Availability of checkpoint inhibitors has created a paradigm shift in the management patients with solid tumors. Despite this, most do not respond to immunotherapy, and there is considerable interest developing combination therapies improve response rates outcomes. B7-H3 (CD276) member B7 family cell surface molecules provides an alternative immune molecule therapeutically target alone or programmed death-1 (PD-1)–targeted therapies. Enoblituzumab, investigational anti-B7-H3...
The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around world. In patients who experience severe disease, acute respiratory distress is often accompanied a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of profound inflammatory state seen in with COVID-19 succumb pneumonia and hypoxia marked elevation serum cytokines, especially interferon gamma, tumor necrosis factor alpha,...
Purpose: Although many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored in vitro response of sarcoma cell lines against a large collection investigational and approved drugs identify candidate combinations.Experimental Design: Drugs displaying activity as single agents were evaluated combinatorial (matrix) format highly active, synergistic drug combinations,...
Abstract De novo and acquired drug resistance can limit the long-term efficacy of targeted cancer therapies such as tyrosine kinase inhibitors targeting key oncogenic drivers like EGFR cMET. Mechanisms include secondary mutations cMET other downstream pathways KRAS amplification alternate growth factor receptors. MET or protein overexpression has been established most common mechanism clinical to osimertinib. AZD9592 is a first-in-class bispecific ADC designed target cMET, while overcoming...
Abstract Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, gene encoding cyclin D, known be amplified a variety of solid tumors. Palbociclib an oral CDK4/6 inhibitor, approved advanced breast cancer combination with endocrine therapy. We explored efficacy palbociclib patients nonbreast tumors containing amplification CCND1, 2, or 3. Patients and Methods: 3 expression retinoblastoma protein were assigned subprotocol Z1B received 125 mg once daily for 21 days...
To identify novel signaling pathways necessary for rhabdomyosarcoma (RMS) survival, we performed a loss-of-function screen using an inducible small hairpin RNA (shRNA) library in alveolar and embryonal RMS cell line. This identified CRKL expression as growth of both vitro vivo. We also found that was uniformly highly expressed lines tumor tissue. As is member the CRK adapter protein family contains SH2 two SH3 domains involved signal transduction from multiple tyrosine kinase receptors,...
Background Immune checkpoint inhibitors have revolutionized the treatment of solid tumors, enhancing clinical outcomes by releasing T cells from inhibitory effects receptors like programmed cell death protein 1 (PD-1). Despite these advancements, achieving durable antitumor responses remains challenging, often due to additional immunosuppressive mechanisms within tumor microenvironment (TME). Tumor-associated macrophages (TAMs) contribute significantly TME and play a pivotal role in shaping...
Abstract Background: Each year an estimated 1.9 million people are diagnosed with colorectal cancer worldwide and approximately 930, 000 die due to mCRC. The TOPO1i irinotecan is used frequently in combination chemotherapy regimens treat mCRC that cannot be managed surgery. Colorectal tumor cells often overexpress the cell membrane proteins epidermal growth factor receptor (EGFR) mesenchymal-epithelial transition tyrosine kinase (cMET). Overexpression of either EGFR or cMET associated...
Abstract Background: AZD9592 is a bispecific ADC designed to target both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition tyrosine kinase (cMET), delivering topoisomerase 1 inhibitor payload tumor cells. Despite recent advances in development for CRC, such as the use of trastuzumab deruxtecan treat HER2-positive significant unmet need remains novel therapeutic approaches, particularly patients with limited targeted treatment options. Methods: We evaluated...
Ewing sarcoma is the second most common pediatric malignant bone tumor. Aggressive multimodality therapy has led to an improvement in outcomes, particularly patients with localized disease. However, therapy-related toxicities are not trivial, and prognosis for relapsed and/or metastatic disease continues be poor. In this article, we outline some of promising therapies that have potential change therapeutic paradigm not-too-distant future: insulin-like growth factor receptor inhibitors,...
Abstract Purpose: Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer–associated carcinoma (HLRCC-RCC), gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, many targeted therapies. We evaluated guadecitabine, a dinucleotide containing the DNA methyltransferase inhibitor decitabine, in...
Abstract AZD9592 is a bispecific antibody drug conjugate (ADC) designed to deliver topoisomerase 1 inhibitor (TOP1i) cytotoxic payload (AZ14170133) tumor cells. selectively binds epidermal growth factor receptor (EGFR) and c-MET, two cell surface receptors highly expressed in solid tumors including non-small-cell lung cancer (NSCLC) head neck squamous carcinoma (HNSCC). Here we evaluate the pharmacodynamic activity of TOP1i delivery by an NSCLC-derived xenograft model using...
Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children wild-type for
TPS3156 Background: The epidermal growth factor receptor (EGFR) and mesenchymal-epidermal transition tyrosine kinase (c-MET) are expressed in diverse solid tumors, function as driver genes some types. Clinical benefit of bispecific monoclonal antibodies (Ab) targeting these receptors was demonstrated pts with EGFR mutated (EGFRm) non-small-cell lung cancer (NSCLC), but an ADC has not been developed. AZD9592 is a Ab c-MET. When internalized, releases topoisomerase 1 inhibitor (TOP1i) warhead...
Abstract Background: NCI-MATCH (EAY 131) assigns patients (pts) with refractory solid tumors, lymphomas, or multiple myeloma to targeted therapies based on somatic alterations identified in fresh tumor biopsies. Arm Z1B examined the cyclin dependent kinase 4 and 6 inhibitor palbociclib pts whose tumors contained CCND1, 2 3 amplification. Methods: Pts containing CCND amplification retinoblastoma (Rb) expression by immunohistochemistry were eligible. breast cancer excluded. received 125mg...
11540 Background: Loss of activity the Krebs cycle component succinate dehydrogenase (SDH) complex is a mechanism tumorigenesis in SDH-deficient cancers. Accumulation metabolite inhibits α-ketoglutarate-dependent dioxygenases leading to DNA hypermethylation. Guadecitabine small molecule methyltransferase inhibitor. We conducted Phase II study test hypothesis that guadecitabine will impact tumor growth by reversing hypermethylation tumors with abnormalities (NCT03165721). Study Objectives:...
TPS2608 Background: Loss of activity Krebs cycle components succinate dehydrogenase (SDH) complex or fumarate hydratase (FH) has been identified as a mechanism tumorigenesis in SDH-deficient gastrointestinal stromal tumor, pheochromocytoma and paraganglioma (PHEO/PGL), hereditary leiomyomatosis renal cell cancer (HLRCC). Accumulation the metabolites inhibits α-ketoglutarate-dependent dioxygenases leading to DNA hypermethylation these tumors. Guadecitabine is small molecule derivative...