A5045387212- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Lung Cancer Research Studies
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Glutathione Transferases and Polymorphisms
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Heat shock proteins research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- HIV/AIDS drug development and treatment
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
APLA Health
2013-2025
University of California, Los Angeles
2009-2024
UCLA Health
2014-2020
Bristol-Myers Squibb (United States)
2019
Black AIDS Institute
2019
UCLA Jonsson Comprehensive Cancer Center
2010-2018
Bayer (United States)
2017
Bayer (Germany)
2017
Novartis (United States)
2016
Ronald Reagan UCLA Medical Center
2014
Alterations in cell cycle regulators have been implicated human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation low nanomolar range. To identify predictors response, we determined vitro sensitivity across a panel molecularly characterized cancer lines.Forty-seven immortalized lines representing known molecular subgroups were treated determine IC50...
Abstract Purpose: Altered PI3K/mTOR signaling is implicated in the pathogenesis of a number breast cancers, including those resistant to hormonal and HER2-targeted therapies. Experimental Design: The activity four classes inhibitory molecules, pan-PI3K inhibitor (NVP-BKM120), p110α isoform–specific PI3K (NVP-BYL719), an mTORC1-specific (NVP-RAD001), dual PI3K/mTORC1/2 (NVP-BEZ235), was evaluated both vitro vivo against panel 48 human cell lines. Results: Each agent showed significant...
Abstract Background Combined targeting of CDK4/6 and ER is now the standard care for patients with advanced ER+/HER2− breast cancer. However, acquired resistance to these therapies frequently leads disease progression. As such, it critical identify mechanisms by which CDK4/6-based also therapeutic strategies overcome resistance. Methods In this study, we developed characterized multiple in vitro vivo models therapies. Resistant were screened reverse phase protein array (RPPA) cell signaling...
Journey to jorumycin Jorumycin is a structurally complex, pentacyclic organic compound produced by marine mollusk. The success of similar compound, trabectedin, in treating certain types cancer has focused attention on exploring jorumycin's pharmaceutical properties. Welin et al. developed succinct route synthesizing and the closely related jorunnamycin A that deliberately diverges from putative biosynthetic pathway underlying prior chemical syntheses. This route, which hinges carefully...
The cyclinD:CDK4/6:Rb axis is dysregulated in a variety of human cancers. Targeting this pathway has proven to be successful therapeutic approach ER+ breast cancer. In study, vitro and vivo preclinical cancer models were used investigate the expanded use CDK4/6 inhibitor, abemaciclib. Using panel 44 cell lines, differential sensitivity abemaciclib was observed seen predominately luminal ER+/HER2- ER+/HER2+ subtypes. However, subset triple-negative (TNBC) lines with intact Rb signaling also...
To improve our understanding of ovarian cancer, we performed genome-wide analyses 45 cancer cell lines. Given the challenges genomic tumors without matched normal samples, developed approaches for detection somatic sequence and structural changes integrated these with epigenetic expression alterations. Alterations not previously implicated in included amplification or overexpression ASXL1 H3F3B, deletion underexpression CDC73 TGF-beta receptor pathway members, rearrangements YAP1-MAML2...
The human EGF (HER) family of receptors has been pursued as therapeutic targets in breast cancer and other malignancies. Trastuzumab lapatinib are standard treatments for HER2-amplified cancer, but a significant number patients do not respond or develop resistance to these drugs. Here we evaluate the vitro activity dacomitinib (PF-00299804), an irreversible small molecule pan-HER inhibitor, large panel cell lines with variable expression HER ligands, sensitivity trastuzumab lapatinib....
Abstract HSP90 enables the activation of many client proteins which most clinically validated is HER2. NVP-AUY922, a potent inhibitor, currently in phase II clinical trials. To explore its potential use HER2-amplified breast and gastric cancers, we evaluated effect AUY922 alone combination with trastuzumab both trastuzumab-sensitive -resistant models. A panel 16 human 45 cancer cell lines, including (3 13, respectively) cells, was treated over various concentrations. In cancer, used lines...
Abstract Poly-adenosine diphosphate (ADP)-ribose polymerase 7 (PARP7) is an enzyme that postranslationally modifies target proteins with ADP-ribose group, which required for multiple cellular processes, including DNA repair, immune function, and metabolism. Recent studies have identified a subset of non-small cell lung cancer (NSCLC) exhibiting dependency to PARP7, suggesting PARP7 may be therapeutic NSCLC. In addition, was recently as evasion mechanism cells escape surveillance by dampening...
Abstract Lung cancer is the leading cause of related deaths worldwide, with non-small cell lung (NSCLC) being most common subtype. Current treatments, including targeted therapy and immunotherapy, only yield durable clinical responses for a subset patients highlighting need new treatment options. Integrins (ITGs) are diverse class heterodimeric, transmembrane receptors that bind to extracellular matrix (ECM) cytoskeleton integrate bi-directional signals between environment interior. Each...
Abstract Poly (ADP‐ribose) polymerase 1 (PARP1) is an enzyme involved in DNA repair under investigation as a chemotherapeutic target. Current randomized phase three trials of PARPi metastatic breast cancer are limited to patients with documented BRCA1/2 mutations and no biomarker beyond BRCA status available. In effort identify novel biomarkers for PARP inhibition, we created cell line (HCC1187/TALRES) resistant the PARP1 inhibitor talazoparib. Herein show by array‐CGH that HCC1187/TALRES...
1099 Background: An urgent problem in breast cancer treatment is the identification and validation of a targeted therapy for triple-negative (TNBC), ie, negative ER, PR HER2. Neratinib low molecular weight irreversible pan-HER inhibitor that selectively targets tyrosine kinase activity EGFR, HER2 HER4. To-date, neratinib has been exclusively investigated HER2-positive tumors. However, as also EGFR expression, we hypothesised it may have clinical efficacy TNBC. Methods: The anti-proliferative...
1054 Background: Currently, one of the most urgent problems in breast cancer therapeutics is validation targeted therapy for triple-negative (TNBC). Neratinib an irreversible small molecule inhibitor that targets kinase activity EGFR, HER2 and HER4. As these targets, expressed at high levels a subset TNBC, we hypothesised neratinib potential treatment least some patients with TNBC. Methods: The antiproliferative effects were investigated panel 35 cells lines including 9 luminal, 12...
Abstract The selective cyclin dependent kinases 4 and 6 (CDK-4/6) inhibitor, palbociclib, has recently been approved in combination with endocrine-based therapies for the treatment of advanced ER+/HER2- breast cancer (BC). Despite improvements progression-free overall survivals, a significant number patients on CDK-4/6 therapy will go to develop progressive disease. As such, it is critical identify mechanisms by which tumor cells evade targeted therapeutic strategies overcome resistance. In...
Abstract Background: Melanoma, a malignancy originating in pigment-producing melanocytes, is generally resistant to conventional treatments such as radiotherapy or chemotherapy. Molecular targeted therapeutics against BRAF and MEK have shown marked efficacy for patients with metastatic melanoma. However these therapies limited duration of response. Palbociclib highly selective inhibitor cyclin dependent kinases 4 6 (CDK4/6) that has been inhibit growth malignant cell lines vitro vivo by...
Abstract BACKGROUND: Aurora kinases (AK) A and B play essential roles in multiple stages of mitosis are frequently overexpressed a subset human cancers, including ovarian cancer (OC). AMG 900, potent highly selective small molecule inhibitor AKs, showed promising single-agent activity heavily pretreated patients with advanced OC Phase 1b clinical trial. In this study, we report the preclinical effects 900 panel well-characterized cell lines representing clinically-relevant subtypes. METHODS:...
Abstract Lung cancer is the leading cause of related deaths worldwide, with most prevalent subtype being non-small cell lung (NSCLC). As only a subset patients exhibits durable clinical responses to current treatments, including targeted therapy and immunotherapy, new treatment options are needed. Integrins (ITGs) diverse class heterodimeric, transmembrane receptors that bind extracellularly extracellular matrix (ECM) intracellularly cytoskeleton integrate signals bi-directionally between...
Abstract Background: Cyclin-dependent kinases (CDKs) play a significant role in regulating cell cycle progression through association with cyclins. CDK4 and CDK6 interact cyclin D1 to mediate hyperphosphorylation of retinoblastoma (Rb) during early G1 phase. Palbociclib is highly selective inhibitor which functions by blocking pRb phosphorylation resulting arrest sensitive lines. We evaluated the effect palbociclib gastric colon cancer lines explore potential biomarkers response guide...