Linda M. Liau
A5079316205- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- CAR-T cell therapy research
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- MRI in cancer diagnosis
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Advanced MRI Techniques and Applications
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Brain Metastases and Treatment
- Circular RNAs in diseases
- Plant biochemistry and biosynthesis
- RNA Interference and Gene Delivery
- Lanthanide and Transition Metal Complexes
- Chromatin Remodeling and Cancer
- Lung Cancer Treatments and Mutations
University of California, Los Angeles
2016-2025
UCLA Health
2013-2024
UCLA Medical Center
2009-2024
UCLA Jonsson Comprehensive Cancer Center
2014-2023
University of Colorado Cancer Center
2017-2023
University of Colorado Denver
2017-2023
Oregon Health & Science University
2023
University of California System
2012-2021
ORCID
2021
APLA Health
2010-2020
The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response EGFR kinase inhibitors. mechanism responsiveness glioblastomas these inhibitors unknown.
Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze genomes are underway, but analysis hampered by lack statistical framework distinguish meaningful events from random background aberrations. Here we describe systematic method, called Genomic Identification Significant Targets in Cancer (GISTIC), designed analyzing chromosomal aberrations cancer. We use it study...
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight need molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify full spectrum of driver genes molecular processes that operate in medulloblastoma subgroups. Here we analyse somatic landscape across 491 sequenced samples heterogeneity among 1,256 epigenetically analysed cases, subgroup-specific...
Abstract In current clinical practice, histology-based grading of diffuse infiltrative gliomas is the best predictor patient survival time. Yet histology provides little insight into underlying biology and limited in its ability to identify guide new molecularly targeted therapies. We have performed large-scale gene expression analysis using Affymetrix HG U133 oligonucleotide arrays on 85 infiltrating all histologic types assess whether a expression-based, histology-independent classifier...
Glioblastoma is the most common primary malignant brain tumor of adults and one lethal all cancers. Patients with this disease have a median survival 15 months from time diagnosis despite surgery, radiation, chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit molecularly targeted therapies. Here, we address compelling need for identification new molecular targets. Leveraging global gene expression data two independent sets clinical...
Background There is much discussion in the cancer drug development community about how to incorporate molecular tools into early-stage clinical trials assess target modulation, measure anti-tumor activity, and enrich trial population for patients who are more likely benefit. Small, molecularly focused studies offer promise of early definition optimal biologic dose patient population. Methods Findings Based on preclinical evidence that phosphatase tensin homolog deleted Chromosome 10 (PTEN)...
Abstract Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell–mediated antitumor immune responses against brain tumors in animal models. As a next step vaccine development, phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic intracranial T-cell patients glioblastoma multiforme. Experimental Design: Twelve were enrolled into multicohort dose-escalation...
Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard newly diagnosed glioblastoma.After surgery chemoradiotherapy, patients were randomized (2:1) receive temozolomide plus DCVax-L (n = 232) or placebo 99). Following recurrence, all allowed DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); secondary...
Purpose This open-label, prospective, multicenter single-arm phase II study combined bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed glioblastoma (GBM). The objectives were to determine efficacy this combination associated toxicity. Patients Methods Seventy patients GBM enrolled between August 2006 November 2008. received standard RT starting within 3 6 weeks after surgery concurrent administration daily TMZ biweekly BV. After...
Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through inclusion molecular subgroup profiles.We determined affiliation, mutation status, and clinical outcome a discovery cohort 397 medulloblastomas. subsequently validated our results on an independent 156 medulloblastomas.TP53 are enriched wingless (WNT; 16%) sonic hedgehog (SHH; 21%) medulloblastomas virtually absent subgroups 3 4 tumors (P < .001). Patients...
Purpose Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1 R132MUT ) is frequent low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, regardless of clinical history. To determine how arising with IDH1 differ other GBMs, we undertook comprehensive comparison patients presenting clinically primary GBM function mutation status. Patients and Methods In all, 618 treatment-naive 235 were...
Abstract Purpose: To assess the feasibility, safety, and toxicity of autologous tumor lysate–pulsed dendritic cell (DC) vaccination toll-like receptor (TLR) agonists in patients with newly diagnosed recurrent glioblastoma. Clinical immune responses were monitored correlated gene expression profiles. Experimental Design: Twenty-three glioblastoma (WHO grade IV) enrolled this dose-escalation study received three biweekly injections glioma lysate-pulsed DCs followed by booster vaccinations...
Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, promote malignant transformation, and appear to be a major determinant response inhibitor therapy. Missense mutations EGFR domain, for example, have recently been identified patients who showed clinical responses therapy.Encouraged by promising activity epidermal growth factor...
Abstract Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions extracellular (EC) domain. Unlike lung cancers with EGFR kinase domain (KD) mutations, GBMs respond poorly to inhibitor erlotinib. Using RNAi, we show that GBM cells carrying EC display addiction. In contrast KD mutants found cancer, glioma-specific are inhibited by inhibitors target active conformation (e.g., erlotinib). Inhibitors bind inactive conformation,...
Development of biofluid-based molecular diagnostic tests for cancer is an important step towards tumor characterization and real-time monitoring in a minimally invasive fashion. Extracellular vesicles (EVs) are released from cells into body fluids can provide powerful platform biomarkers because they carry proteins nucleic acids. Detecting rare point mutations the background wild-type sequences biofluids such as blood cerebrospinal fluid (CSF) remains major challenge. Techniques BEAMing...
Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, histologic variant. Stark prognostic genetic differences among the subgroups suggest that subgroup-specific biomarkers could improve prognostication.Molecular were identified from a discovery set 673 medulloblastomas 43 cities around world. Combined risk stratification models...