Andrew J Brenner, MD, PhD

• Professional Background

  Education

  • 2003 - MD - Medicine - Texas Tech University Health Science Center School of Medicine
  • 1997 - PhD - Tumor Biology - University of Texas at Austin / MD Anderson Cancer Center Science Park
  • 1993 - BS - Biochemistry - Texas A&M University
  • Residency - Internal Medicine - Texas A&M University Health Science Center at Scott and White Memorial Hosp
  • Clinical Fellowship - Medical Oncology - University of Texas Health Science Center at San Antonio
  • Postdoctoral Fellowship - European Institute of Oncology
  • Postdoctoral Fellowship - UT M. D. Anderson Cancer Center Science Park

  Appointments

  • 7/2015 - Associate Professor, Tenured and CTRC Medical Director - UT Health San Antonio Cancer CenterSan Antonio
  • 5/2011 - Adjunct Assistant Professor - University of Texas at Austin, Nutritional Sciences, Austin

• Instruction & Training

  • 12/2008 - Present, Research, The University of Texas Health Science Center
  • 7/2008 - Present, Medical Oncology Lecture Series, UTHSCSA, Fellowship Program

• Research & Grants

  Animal Models, Breast Cancer, Clinical Trials, Neuro-Oncology, Phase I

  Co-Leader, Experimental and Developmental Therapeutics Program 

  Research profile

  Grants

  Federal

  Funding Agency National Cancer Institute Title Novel ERbeta agonists for the treatment of gliomas Status Active Period 8/2014 - 7/2019 Role Principal Investigator Grant Detail   Funding Agency Food and Drug Administration Title Efficacy of TH-302, with Molecular Imaging and Biomarker Correlates of Response in Bevacizumab Resistant Glioblastoma Status Active Period 8/2014 - 7/2018 Role Principal Investigator Grant Detail Glioblastoma (GBM) is the most common and most aggressive of the primary malignant brain tumors in adults. Annually there are approximately 13,000 cases of GBM diagnosed, with historical 1 year and 5 year survival rates of 34.6% and 4.75%. While concomitant chemoradiotherapy with temozolomide remains the standard of care for initial treatment, all patients eventually require salvage therapy, and angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) pathway are standard in this setting. The proposed study is a dual center, single-arm, non-blinded, prospective study of combination therapy bevacizumab and TH-302 in up to 33 GBM patients. Bevacizumab will be administered at 10mg/kg as established standard of care. The planned dose for TH-302 is 480mg/m2 every 2 weeks (6 week cycle) until disease progression. The primary endpoint is the proportion progression-free at 4 months, with secondary end points of median progression-free survival (PFS), median overall survival (OS), safety, and quality of life (QOL). The three specific aims are to: 1) establish the efficacy of TH-302 in GBM patients progressing on bevacizumab, 2) characterize hypoxic volume, cerebral blood flow, and oxygen extraction fraction (OEF) in patients undergoing treatment with TH-302, and 3) correlate changes in known molecular markers of bevacizumab de novo resistance, acquired resistance, and tumor hypoxia with tumor response, time to progression, and patient survival.

  State

  Funding Agency CPRIT Title NanoTx Therapeutics New Company Product Development Award Status Active Period 5/2015 - 1/2018 Role Principal Investigator Grant Detail Funds are made available to support the establishment of a new company with the goal of development and commercialization of liposomally encapsulated therapeutic radionuclides for the treatment of cancer, Funding Agency Cancer Prevention & Research Institute of Texas Title Overcoming CXCL12 Mediated Resistance in Glioblastoma Status Active Period 12/2013 - 12/2017 Role Principal Investigator Grant Detail The most significant recent advance for glioblastoma has been the application of antiangiogenic agents. Unfortunately, more than half of these tumors are de novo resistant and all eventually develop resistance when initially sensitive. Evidence points to the root cause of angiogenesis, hypoxia, as a driving force for resistance to anitangiogenics. The chemokine CXCL12 is strongly induced by HIF-1a under conditions of hypoxia, and in clinical trials of antiangiogenic agents, serum levels of CXCL12 significantly increase with disease progression and mark resistance to therapy. While CXCR4 was once thought to be CXCL12?s sole receptor, more recently CXCR7 was deorphanized and appears to mediate a number of CXCL12 dependent normal physiologic processes. Of relevance to anitangiogenic resistance, one process that CXCR7 is involved in is maintaining survival of neural progenitor cells under conditions of hypoxia induced by stroke. Further along these lines, data supports a possible role for CXCR7 in preventing apoptosis of glioma cells when exposed to alkylator chemotherapy. Thus, newer data seems to support that the rise in CXCL12 in patients serum at the time of progression on antiangiogenics is more than coincidental, and further that CXCR7 rather than CXCR4 may be in part mediating antiangiogenic resistance in these patients. In our own studies in orthotopic glioblastoma xenografts receiving a monoclonal antibody against vascular endothelial growth factor (VEGF), we found that animals had increased survival when treated concomitantly with CXCR7 inhibitor CCX771. No improvement in survival was seen with the use of CXCR4 inhibitor AMD3100, despite confirmation that adequate tissue penetration across the blood brain barrier was present as well as presence of CXCR4 expression within the tumor and tumor endothelium. These findings, as well as emerging roles for CXCR7 in survival of progenitor cells, has led us to hypothesize that CXCL12 receptors CXCR4 and CXCR7 have uniqu

• Publications

  • Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Di
  • Circulating metabolites associated with tumor hypoxia and early response to treatment in bevacizumab-refractory glioblastoma af
  • Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors
  • The antidepressant imipramine inhibits breast cancer growth by targeting estrogen receptor signaling and DNA repair events
  • ELF4 is a critical component of a miRNA-transcription factor network and is a bridge regulator of glioblastoma receptor signalin
  • Targeting aberrant replication and DNA repair events for treating breast cancers
  • Supratentorial ependymoma, zinc finger translocation-associated fusion positive, with extensive synaptophysin immunoreactivity a
  • Global DNA methylation profiling reveals chromosomal instability in IDH-mutant astrocytomas
  • Differentiation of Brain Tumor Microvasculature From Normal Vessels Using Optical Coherence Angiography
  • LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer
  • Preservation of quality of life in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer trea
  • Histone deacetylase inhibitors enhance estrogen receptor beta expression and augment agonist-mediated tumor suppression in gliob
  • Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA5
  • Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 i
  • FASN inhibition as a potential treatment for endocrine-resistant breast cancer
  • Patient specific, imaging-informed modeling of rhenium-186 nanoliposome delivery via convection-enhanced delivery in glioblastom
  • Activation of estrogen receptor beta signaling reduces stemness of glioma stem cells
  • Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET
  • First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2
  • Interaction of transcription factor AP-2 gamma with proto-oncogene PELP1 promotes tumorigenesis by enhancing RET signaling
  • The Impact of Surgery on the Survival of Patients with Recurrent Glioblastoma
  • Math, magnets, and medicine: enabling personalized oncology
  • Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma
  • KDM1A inhibition is effective in reducing stemness and treating triple negative breast cancer
  • Evaluating the Impact of Omega-3 Free Fatty Acid Supplementation on Postoperative Complications in Obese Postmenopausal Women Wi
  • ANG1005, a Brain-Penetrating Peptide-Drug Conjugate, Shows Activity in Patients with Breast Cancer with Leptomeningeal Carcinoma
  • A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurren
  • Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II stud
  • Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours
  • Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression
  • PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway
  • Primary CNS lymphoma commonly expresses immune response biomarkers
  • Stable Isotope Dilution LC-HRMS Assay To Determine Free SN-38, Total SN-38, and SN-38G in a Tumor Xenograft Model after Intraven
  • Tumor Mutational Burden Is Site Specific in Non-Small-Cell Lung Cancer and Is Highest in Lung Adenocarcinoma Brain Metastases
  • PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling
  • Temozolomide as a Single Agent Maintenance Therapy in Elderly Patients With Primary CNS Lymphoma
  • EC359: A First-in-Class Small-Molecule Inhibitor for Targeting Oncogenic LIFR Signaling in Triple-Negative Breast Cancer
  • The current state of molecular testing in the treatment of patients with solid tumors, 2019
  • BRCA1-associated R-loop affects transcription and differentiation in breast luminal epithelial cells
  • Laser brain cancer surgery in a xenograft model guided by optical coherence tomography
  • Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways
  • Evaluating Multisite rCBV Consistency from DSC-MRI Imaging Protocols and Postprocessing Software Across the NCI Quantitative Ima
  • MiR-584-5p potentiates vincristine and radiation response by inducing spindle defects and DNA damage in medulloblastoma
  • Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial
  • Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study
  • Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly di
  • Differential Effects of Estrogen Receptor β Isoforms on Glioblastoma Progression
  • First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed gliobla
  • Primary Diffuse Large B-Cell Lymphoma in a Patient with Rubinstein-Taybi Syndrome: Case Report and Review of the Literature
  • Metabolomic signature of brain cancer
  • Therapeutic utility of natural estrogen receptor beta agonists on ovarian cancer
  • Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway
  • Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors
  • PELP1: Structure, biological function and clinical significance
  • Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma
  • Hypoxia in astrocytic tumors and implications for therapy
  • Obesity Suppresses Estrogen Receptor Beta Expression in Breast Cancer Cells via a HER2-Mediated Pathway
  • Cancer therapy using natural ligands that target estrogen receptor beta
  • Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique
  • VB-111: a novel anti-vascular therapeutic for glioblastoma multiforme
  • Osteolytic calvarial lesions as initial presentation of latent neurosyphilis
  • Activity of 2-aryl-2-(3-indolyl)acetohydroxamates against drug-resistant cancer cells
  • Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostagla
  • Predicting success in regulatory approval from Phase I results
  • Clinical outcomes and survival of advanced renal cancer patients in phase I clinical trials
  • Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles
  • NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions
  • Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors
  • The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are rever
  • Phase I study of GRN1005 in recurrent malignant glioma
  • Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and MAPK pathways to promote in vitro measures of brea
  • KDM1 is a novel therapeutic target for the treatment of gliomas
  • Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma
  • Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, an
  • The oncogenic RNA-binding protein Musashi1 is regulated by HuR via mRNA translation and stability in glioblastoma cells
  • The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs
  • A prospective randomised study of a rotary powered device (OnControl) for bone marrow aspiration and biopsy
  • Powered bone marrow biopsy procedures produce larger core specimens, with less pain, in less time than with standard manual devi
  • Common toxicities of mammalian target of rapamycin inhibitors
  • Rotary powered device for bone marrow aspiration and biopsy yields excellent specimens quickly and efficiently
  • RANK ligand: effects of inhibition
  • Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma
  • Heterogeneity in the effect of albumin and other resuscitation fluids on intracellular oxygen free radical production
  • WWOX, the FRA16D gene, behaves as a suppressor of tumor growth
  • Increased p16 expression with first senescence arrest in human mammary epithelial cells and extended growth capacity with p16 in
  • Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage
  • The genetics of sporadic breast cancer
  • Preferential loss of expression of p16(INK4a) rather than p19(ARF) in breast cancer
  • Chromosome 9p allelic loss and p16/CDKN2 in breast cancer and evidence of p16 inactivation in immortal breast epithelial cells
  • A quantitative test for copper using bicinchoninic acid

• Clinical

  Board Certifications

  • American Board of Internal Medicine/Oncology