Andrew J Brenner, M.D.
Cell Systems and Anatomy
A specialist in both breast cancer and malignancies of the brain and spinal cord, Dr. Andrew Brenner not only focuses on clinical management, but also on the development of novel therapies to treat breast cancers and central nervous system tumors. A graduate of Texas A&M University, he earned his bachelor’s degree in biochemistry and went on to earn his doctorate in biological science and tumor biology at The University of Texas M.D. Anderson Cancer Center - Science Park. His doctoral thesis focused on the role of the cyclin dependent kinase inhibitor p16INK4a in mammary tumorigenesis and immortilization. Dr. Brenner’s current interests have transitioned from cell cycle to the effect of hypoxia on chemokines and escape from antiangiogenics and the role of obesity in promoting breast tumorigenesis. Dr. Brenner received his medical degree from the Texas Tech University Health Science Center and completed a residency in internal medicine at Scott and White Hospital in Lubbock. He completed his fellowship in hematology and medical oncology at the UT Health San Antonio.
Aksenov, A. V., Smirnov, A. N., Magedov, I. V., Reisenauer, M. R., Aksenov, N. A., Aksenova, I. V., Pendleton, A. L., Nguyen, G., Johnston, R. K., Rubin, M., De Carvalho, A., Kiss, R., Mathieu, V., Lefranc, F., Correa, J., Cavazos, D. A., Brenner, A. J., Bryan, B. A., Rogelj, S., Kornienko, A. & Frolova, L. V. Activity of 2-Aryl-2-(3-indolyl)acetohydroxamates against Drug-Resistant Cancer Cells. J. Med. Chem. 12;58(5):2206-20 (2015). PMID: 25671501
Bowers, L. W., Brenner, A. J., Hursting, S. D., Tekmal, R. R. & deGraffenried, L. A. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production. Breast Cancer Res. Treat. 149(1):49-57 (2014). PMID: 25476497; PMCID: PMC4409140
Bowers, L. W., Maximo, I. X., Brenner, A. J., Beeram, M., Hursting, S. D., Price, R. S., Tekmal, R. R., Jolly, C. A. & deGraffenried, L. A. NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin-Aromatase Interactions. Cancer Res. 74, 4446-4457 (2014). PMID: 25125682
- 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
- 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
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.
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
Sareddy GR, Viswanadhapalli S, Surapaneni P, Suzuki T, Brenner A, Vadlamudi RK. Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway Oncogene 2017 Apr;36(17):2423-2434. Beg MS, Brenner AJ, Sachdev J, Borad M, Kang YK, Stoudemire J, Smith S, Bader AG, Kim S, Hong DS. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors Invest New Drugs 2017 Apr;35(2):180-188. Henry S, Kidner R, Reisenauer MR, Magedov IV, Kiss R, Mathieu V, Lefranc F, Dasari R, Evidente A, Yu X, Ma X, Pertsemlidis A, Cencic R, Pelletier J, Cavazos DA, Brenner AJ, Aksenov AV, Rogelj S, Kornienko A, Frolova LV. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells European Journal of Medicinal Chemistry 2016 May;120:313-328. Sareddy GR, Li X, Liu J, Viswanadhapalli S, Garcia L, Gruslova A, Cavazos D, Garcia M, Strom AM, Gustafsson JA, Tekmal RR, Brenner A, Vadlamudi RK. Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma Scientific Reports 2016 Apr;6. Brenner AJ. Hypoxia in astrocytic tumors and implications for therapy Neurobiol Dis 2016 Jan;85:227-233. Brenner AJ. Obesity Suppresses Estrogen Receptor Beta Expression in Breast Cancer Cells via a HER2-Mediated Pathway PLoS One 2015 Dec;10(12). Brenner AJ. Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of primary amines Bioorg Med Chem Lett 2015 Oct;25(20):4544-4548. Brenner AJ. VB-111: a novel anti-vascular therapeutic for glioblastoma multiforme J Neurooncology 2015 Sep;124(3):365-372. Son C, Samples D, Brenner AJ, Floyd JR. Osteolytic calvarial lesions as initial presentation of latent neurosyphilis J Clin Neurosci 2015 May;22(5):909-910. Brenner AJ. Activity of 2-aryl-2-(3-indolyl)acetohydroxamates against drug-resistant cancer cells J Med Chem 2015 Mar;58(5):2206-2220. Bowers LW, Brenner AJ, Hursting SD, Tekmal RR, deGraffenried LA. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production Breast Cancer Res Treat 2015 Jan;149(1):49-57. Malik L, Mejia A, Parsons HM, Ehler B, Mahalingam D, Sarantopoulos J, Brenner AJ, Weitman SD. Predicting success in regulatory approval from Phase I results Cancer Chemother Pharmacol 2014 Nov;74(5):1099-1103. Brenner AJ. Protein imprinting in polyacrylamide-based gels Biomaterials 2014 Oct;35(30):8659-68. Brenner AJ. NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions Cancer Res 2014 Aug;74(16):4446-4457. Bowers, LW, Maximo IX, Brenner AJ, Beeram M, Husrtin SD, Price RS, Tekmal RR, Jolly CA, deGraffenried LA. NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin-Aromatase Interactions Cancer Research 2014 Aug;74(16). Malik L
Sarantopoulos J. Clinical Outcomes and Survival of Advanced Renal Cancer Patients in Phase I Clinical Trial Clin Genitourin Cancer 2014 Feb;(14):19-26. Brenner AJ, Cohen YC, Breitbart E, Bangio L, Sarantopoulos J, Giles FJ, Borden EC, Harats D, Triozzi PL.
. Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors Clin Cancer Res 2013 Jul;19(14):3996-4007. De Angel RE, Conti CJ, Wheatley KE, Brenner AJ, Otto G, Degraffenried LA, Hursting SD.
. The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are reversed by RAD001 Mol Carcinog 2013 Jun;52(6):446-458.
Drappatz J, Brenner A, Wong ET, Eichler A, Schiff D, Groves MD, Mikkelsen T, Rosenfeld S, Sarantopoulos J, Meyers CA, Fielding RM, Elian K, Wang X, Lawrence B, Shing M, Kelsey S, Castaigne JP, Wen PY, Brenner AJ. Phase I study of GRN1005 in recurrent malignant glioma Clin Cancer Res 2013 Mar;19(6):1567-1576. Sareddy GR, Nair BC, Krishnan SK, Gonugunta VK, Zhang QG, Suzuki T, Miyata N, Brenner AJ, Brann DW, Vadlamudi RK. KDM1 is a novel therapeutic target for the treatment of gliomas Oncotarget 2013 Jan;4(1):18-28. Phillips WT, Goins B, Bao A, Vargas D, Guttierez JE, Trevino A, Miller JR, Henry J, Zuniga R, Vecil G, Brenner AJ. Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma Neuro Oncol. 2012 Apr;14(4):416-25. Epub 2012 Mar 16 2012 Apr;14(4):416-425. Kurzrock R, Gabrail N, Chandhasin C, Moulder S, Smith C, Brenner A, Sankhala K, Mita A, Elian K, Bouchard D, Sarantopoulos J. Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors Mol Cancer Ther 2012 Feb;11(2):308-316. Vo DT, Abdelmohsen K, Martindale JL, Qiao M, Tominaga K, Burton TL, Gelfond JA, Brenner AJ, Patel V, Trageser D, Scheffler B, Gorospe M, Penalva LO. The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells Mol Cancer Res 2012 Jan;10(1):143-155. Swords RT, Anguita J, Higgins RA, Yunes AC, Naski M, Padmanabhan S, Kelly KR, Mahalingam D, Philbeck T, Miller L, Puga TA, Giles FJ, Kinney MC, Brenner AJ. A prospective randomised study of a rotary powered device (OnControl) for bone marrow aspiration and biopsy J Clin Pathol 2011 Sep;64(9):809-813. Vo DT, Qiao M, Smith AD, Burns SC, Brenner AJ, Penalva LO. The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs RNA Biol 2011 Sep;8(5). Miller LJ, Philbeck TE, Montez DF, Puga TA, Brodie KE, Cohen SC, Spadaccini C, Swords R, Brenner AJ. Powered bone marrow biopsy procedures produce larger core specimens, with less pain, in less time than with standard manual devices Hematol Rep 2011 Jan;3(1). Swords RT, Kelly KR, Cohen SC, Miller LJ, Philbeck TE, Hacker SO, Spadaccini CJ, Giles FJ, Brenner AJ. Rotary powered device for bone marrow aspiration and biopsy yields excellent specimens quickly and efficiently J Clin Pathol 2010 Jun;63(6):562-565. George S, Brenner A, Sarantopoulos J, Bukowski RM. RANK ligand: effects of inhibition Curr Oncol Rep 2010 Mar;12(2):80-86.
Pandey R, Caflisch L, Lodi A, Brenner AJ, Tiziani S. Metabolomic signature of brain cancer Mol Carcinog 2017 Jun;.
Phillips WT, Bao A, Brenner AJ, Goins BA. Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles Adv Drug Deliv Rev 2014 Sep;76C:39-59.
- American Board of Internal Medicine/Oncology