Thomas C Chen, MD, PhD

Dr. Chen’s goal is to make USC Neuro-oncology the leader in innovative treatments for brain and spine tumors. As a result, emphasis is placed on translating new findings made in the laboratory to clinical trials. Laboratory efforts are directed toward research on endoplasmic reticulum stress, understanding glioblastoma endothelial cells, and development of novel anti-invasion therapies such as vicrostatin, a unique disintegrin made at USC, and noscopine. Technological advances that may be used in the treatment of brain or spine tumors are being developed, patented, and will soon be highlighted. Novel clinical trials currently available or soon to be available at USC include anti-EGFRviii vaccine therapy, IL-4-pseudomonas exotoxin for convection enhanced delivery, and anti-tenascin brachytherapy. Surgical therapy is based on the newest techniques in microdissection and image guidance using neuronavigational therapy, with a soon to be added intraoperative MRI scanner. Spine oncology is especially unique as Dr. Chen is one of the few fellowship trained spine surgeons focused on spine cancer. Decisions on therapy are made through tumor board via a multi-disciplinary team dedicated to neuro-oncology including neurosurgery, medical oncology, radiation oncology, neuropathology, and neuro-radiology.

• Development of NEO212, A Novel Oral Drug for the Treatment of Acute Myeloid Leukemia
  NIH · R41CA271879 · Aug 7, 2025 – Jul 31, 2026 · Role: Principal Investigator
• Developing a Clinically Relevant Radiosensitizer for Temozolomide-resistant Gliomas
  NIH · R42CA246902 · Apr 1, 2020 – Aug 31, 2027 · Role: Principal Investigator
• Developing a clinically relevant radiosensitizer for temozolomide-resistant gliomas
  NIH · R41CA246902 · Apr 1, 2020 – Mar 31, 2021 · Role: Principal Investigator
• Innovative Nose-to-Brain Anticancer Drug Transport Facilitated by NEO100
  NIH · R41CA217551 · Apr 1, 2018 – Mar 31, 2020 · Role: Principal Investigator
• Temozolomide Perillyl Alcohol Conjugate as Treatment for Recurrent Malignant Brain tumors
  NIH · R41CA192419 · Jul 1, 2016 – Jun 30, 2017 · Role: Principal Investigator
• A Novel Brachytherapy Agent for GBM
  NIH · R41CA165626 · Aug 29, 2013 – Jul 28, 2015 · Role: Principal Investigator

• Safety and functional evaluation of a synthetic lamina cover that replaces lost autologous spinal bone after laminectomy, in a sheep and human study. N Am Spine Soc J. 2025 Dec; 24:100795.. View in PubMed
• Results of the ACCOuNT Trial: A Multi-Institutional Prospective Pharmacogenomics Implementation Trial for African American Inpatients. Clin Pharmacol Ther. 2026 01; 119(1):109-119.. View in PubMed
• Potent Therapeutic Activity of NEO212 in Preclinical Models of Human and Canine Leukaemia and Lymphoma. Vet Comp Oncol. 2025 Sep; 23(3):412-423.. View in PubMed
• Care Team Attributes Predict Likelihood of Utilizing Pharmacogenomic Information During Inpatient Prescribing. Clin Transl Sci. 2025 04; 18(4):e70193.. View in PubMed
• Patient with recurrent grade 4 astrocytoma responding favorably to intranasal delivery of NEO100, highly pure perillyl alcohol: illustrative case. J Neurosurg Case Lessons. 2025 Mar 17; 9(11).. View in PubMed
• Water outage predictions for natural hazards using synthetic water distribution systems. Risk Anal. 2025 Aug; 45(8):2116-2131.. View in PubMed
• Bringing intranasal drug delivery for malignancies in the brain to market. Expert Opin Drug Deliv. 2025 Mar; 22(3):311-314.. View in PubMed
• Automated patient selection and care coaches to increase advance care planning for patients with cancer. J Natl Cancer Inst. 2025 Feb 01; 117(2):296-302.. View in PubMed
• Erratum. Inhibition of motility by NEO100 through the calpain-1/RhoA pathway. J Neurosurg. 2024 11 29; 142(4):1203-1204.. View in PubMed
• In Reply: Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model. Neurosurgery. 2025 Feb 01; 96(2):e34.. View in PubMed
• Characterization of cerebrospinal fluid markers as indicators of spinal cord ischemia following an endovascular aortic aneurysm repair procedure. J Neurosurg. 2025 Apr 01; 142(4):993-1002.. View in PubMed
• Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model. Neurosurgery. 2025 Feb 01; 96(2):471-478.. View in PubMed
• Therapeutic effect of NEO400, perillyl alcohol conjugated to linoleic acid, in a mouse model of UV-induced skin damage. Photochem Photobiol. 2025 Mar-Apr; 101(2):338-349.. View in PubMed
• HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages. Nat Commun. 2024 Jun 29; 15(1):5514.. View in PubMed
• Existing knowledge, myths, and perceptions about hepatitis B and liver cancer within highly impacted immigrant communities. J Virus Erad. 2024 Jun; 10(2):100379.. View in PubMed
• NEO212, temozolomide conjugated to NEO100, exerts superior therapeutic activity over temozolomide in preclinical chemoradiation models of glioblastoma. Neurooncol Adv. 2024 Jan-Dec; 6(1):vdae095.. View in PubMed
• MicroRNA-133b Dysregulation in a Mouse Model of Cervical Contusion Injury. Int J Mol Sci. 2024 Mar 06; 25(5).. View in PubMed
• Activation of Epstein-Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide. Cancers (Basel). 2024 Feb 26; 16(5).. View in PubMed
• Enhancing brain entry and therapeutic activity of chimeric antigen receptor T cells with intra-arterial NEO100 in a mouse model of CNS lymphoma. J Neurosurg. 2024 06 01; 140(6):1549-1557.. View in PubMed
• Reduced non-CpG methylation is a potential epigenetic target after spinal cord injury. Neural Regen Res. 2023 Nov; 18(11):2489-2496.. View in PubMed
• A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength. Front Oncol. 2023; 13:1156843.. View in PubMed
• Using machine learning and big data for the prediction of venous thromboembolic events after spine surgery: A single-center retrospective analysis of multiple models on a cohort of 6869 patients. J Craniovertebr Junction Spine. 2023 Jul-Sep; 14(3):221-229.. View in PubMed
• Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate. Autophagy. 2023 12; 19(12):3169-3188.. View in PubMed
• From the groin to the brain: a transfemoral path to blood-brain barrier opening. Oncotarget. 2023 05 04; 14:413-416.. View in PubMed
• Intranasal Delivery of miR133b in a NEO100-Based Formulation Induces a Healing Response in Spinal Cord-Injured Mice. Cells. 2023 03 18; 12(6).. View in PubMed
• Enhanced brain entry of checkpoint-inhibitory therapeutic antibodies facilitated by intraarterial NEO100 in mouse models of brain-localized malignancies. J Neurosurg. 2023 09 01; 139(3):822-830.. View in PubMed
• NEO212, a Perillyl Alcohol-Temozolomide Conjugate, Triggers Macrophage Differentiation of Acute Myeloid Leukemia Cells and Blocks Their Tumorigenicity. Cancers (Basel). 2022 Dec 09; 14(24).. View in PubMed
• Detection of perillyl alcohol and its metabolite perillic acid in postsurgical glioblastoma tissue after intranasal administration of NEO100: illustrative case. J Neurosurg Case Lessons. 2022 Aug 22; 4(8).. View in PubMed
• A Prospective, Cohort Study of SITOIGANAP to Treat Glioblastoma When Given in Combination With Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Nivolumab or Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Pembrolizumab in Patients Who Failed Prior Treatment With Surgical Resection, Radiation, and Temozolomide. Front Oncol. 2022; 12:934638.. View in PubMed
• 5-Aminolevulinic acid-enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up. J Neurosurg. 2022 Nov 01; 137(5):1378-1386.. View in PubMed
• Lumbar surgical drains do not increase the risk of infections in patients undergoing spine surgery. Eur Spine J. 2022 07; 31(7):1775-1783.. View in PubMed
• The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers. Pharmaceutics. 2021 Dec 16; 13(12).. View in PubMed
• Applicability of Pharmacogenomically Guided Medication Treatment during Hospitalization of At-Risk Minority Patients. J Pers Med. 2021 Dec 10; 11(12).. View in PubMed
• Corrigendum to: Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. Neuro Oncol. 2021 Dec 01; 23(12):2123.. View in PubMed
• Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles. Cureus. 2021 Nov; 13(11):e19573.. View in PubMed
• Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. Neuro Oncol. 2021 10 01; 23(10):1656-1667.. View in PubMed
• Medulloblastoma uses GABA transaminase to survive in the cerebrospinal fluid microenvironment and promote leptomeningeal dissemination. Cell Rep. 2021 Jul 27; 36(4):109475.. View in PubMed
• Potentially Curative Therapeutic Activity of NEO212, a Perillyl Alcohol-Temozolomide Conjugate, in Preclinical Cytarabine-Resistant Models of Acute Myeloid Leukemia. Cancers (Basel). 2021 Jul 06; 13(14).. View in PubMed
• Medulloblastoma uses GABA transaminase to survive in the cerebrospinal fluid microenvironment and promote leptomeningeal dissemination. Cell Rep. 2021 06 29; 35(13):109302.. View in PubMed
• Utilization of Discarded Surgical Tissue from Ultrasonic Aspirators to Establish Patient-Derived Metastatic Brain Tumor Cells: A Guide from the Operating Room to the Research Laboratory. Curr Protoc. 2021 Jun; 1(6):e140.. View in PubMed
• In vivo CRISPR screening for novel noncoding RNA functional targets in glioblastoma models. J Neurosci Res. 2021 09; 99(9):2029-2045.. View in PubMed
• Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. Neurooncol Adv. 2021 Jan-Dec; 3(1):vdab005.. View in PubMed
• NEO100 enables brain delivery of blood‒brain barrier impermeable therapeutics. Neuro Oncol. 2021 01 30; 23(1):63-75.. View in PubMed
• Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice. Neurooncol Adv. 2020 Jan-Dec; 2(1):vdaa160.. View in PubMed
• Developing a clinically relevant radiosensitizer for temozolomide-resistant gliomas. PLoS One. 2020; 15(9):e0238238.. View in PubMed
• miR-18a Inhibits BMP4 and HIF-1α Normalizing Brain Arteriovenous Malformations. Circ Res. 2020 10 09; 127(9):e210-e231.. View in PubMed
• Preclinical studies of a novel snake venom-derived recombinant disintegrin with antitumor activity: A review. Biochem Pharmacol. 2020 11; 181:114149.. View in PubMed
• Efficacy of long-term topical flurbiprofen in limiting lens capsule opacities following phacoemulsification in dogs. Vet Ophthalmol. 2020 Jul; 23(4):714-720.. View in PubMed
• Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative. Am J Med. 2020 05; 133.. View in PubMed
• Intravenous delivery of microRNA-133b along with Argonaute-2 enhances spinal cord recovery following cervical contusion in mice. Spine J. 2020 07; 20(7):1138-1151.. View in PubMed
• Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model. Int J Mol Sci. 2020 Feb 20; 21(4).. View in PubMed
• Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats. Drug Test Anal. 2020 Feb; 12(2):268-279.. View in PubMed
• Association Between Outdoor Air Pollution and Risk of Malignant and Benign Brain Tumors: The Multiethnic Cohort Study. JNCI Cancer Spectr. 2020 Apr; 4(2):pkz107.. View in PubMed
• Cytotoxic impact of a perillyl alcohol-temozolomide conjugate, NEO212, on cutaneous T-cell lymphoma in vitro. Ther Adv Med Oncol. 2019; 11:1758835919891567.. View in PubMed
• Sodium Valproate Reduces Neuronal Apoptosis in Acute Pentylenetetrzole-Induced Seizures via Inhibiting ER Stress. Neurochem Res. 2019 Nov; 44(11):2517-2526.. View in PubMed
• Inhibition of motility by NEO100 through the calpain-1/RhoA pathway. J Neurosurg. 2020 10 01; 133(4):1020-1031.. View in PubMed
• NEO212 induces mitochondrial apoptosis and impairs autophagy flux in ovarian cancer. J Exp Clin Cancer Res. 2019 Jun 07; 38(1):239.. View in PubMed
• Efficient brain targeting and therapeutic intracranial activity of bortezomib through intranasal co-delivery with NEO100 in rodent glioblastoma models. J Neurosurg. 2020 03 01; 132(3):959-967.. View in PubMed
• The Rolipram-Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway. Mol Cancer Ther. 2019 03; 18(3):517-530.. View in PubMed
• Distribution of cancer stem cells in two human brain gliomas. Oncol Lett. 2019 Feb; 17(2):2123-2130.. View in PubMed
• NEO412: A temozolomide analog with transdermal activity in melanoma in vitro and in vivo. Oncotarget. 2018 Dec 11; 9(97):37026-37041.. View in PubMed
• Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development. Int J Mol Sci. 2018 Dec 06; 19(12).. View in PubMed
• A Novel Venom-Derived Peptide for Brachytherapy of Glioblastoma: Preclinical Studies in Mice. Molecules. 2018 Nov 08; 23(11).. View in PubMed
• Bioorthogonal Profiling of a Cancer Cell Proteome Identifies a Large Set of 3-Bromopyruvate Targets beyond Glycolysis. ACS Chem Biol. 2018 11 16; 13(11):3054-3058.. View in PubMed
• NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma. Cancer Lett. 2019 02 01; 442:170-180.. View in PubMed
• Temozolomide-Perillyl alcohol conjugate impairs Mitophagy flux by inducing lysosomal dysfunction in non-small cell lung Cancer cells and sensitizes them to irradiation. J Exp Clin Cancer Res. 2018 Oct 16; 37(1):250.. View in PubMed
• Rare Stochastic Expression of O6-Methylguanine- DNA Methyltransferase (MGMT) in MGMT-Negative Melanoma Cells Determines Immediate Emergence of Drug-Resistant Populations upon Treatment with Temozolomide In Vitro and In Vivo. Cancers (Basel). 2018 Sep 28; 10(10).. View in PubMed
• Therapeutic Immunization against Glioblastoma. Int J Mol Sci. 2018 Aug 27; 19(9).. View in PubMed
• Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts. CNS Oncol. 2018 07 01; 7(3):CNS22.. View in PubMed
• NEO212: sub-cytotoxic doses capable of inhibiting glioma stem cell invasion. Oncoscience. 2018 May; 5(5-6):148-149.. View in PubMed
• Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Apr 01; 4(4):495-504.. View in PubMed
• NEO212 Inhibits Migration and Invasion of Glioma Stem Cells. Mol Cancer Ther. 2018 03; 17(3):625-637.. View in PubMed
• Temozolomide-perillyl alcohol conjugate downregulates O6-methylguanin DNA methltransferase via inducing ubiquitination-dependent proteolysis in non-small cell lung cancer. Cell Death Dis. 2018 02 09; 9(2):202.. View in PubMed
• Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells by NEO214, Perillyl Alcohol Conjugated to Rolipram. Int J Mol Sci. 2018 Jan 17; 19(1).. View in PubMed
• Spine Surgery Complicated by an Engorged Lumbar Epidural Venous Plexus from Cerebrospinal Fluid Overshunting: A Case Report and Review of the Literature. World Neurosurg. 2018 Mar; 111:68-72.. View in PubMed
• Transpedicular Corpectomy and Cage Placement in the Treatment of Traumatic Lumbar Burst Fractures. Clin Spine Surg. 2017 Oct; 30(8):360-366.. View in PubMed
• A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells. Cancer Lett. 2017 08 01; 400:161-174.. View in PubMed
• Intratumoral delivery of bortezomib: impact on survival in an intracranial glioma tumor model. J Neurosurg. 2018 03; 128(3):695-700.. View in PubMed
• Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and α6β1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties. Front Cell Neurosci. 2016; 10:284.. View in PubMed
• Targeting Notch enhances the efficacy of ERK inhibitors in BRAF-V600E melanoma. Oncotarget. 2016 11 01; 7(44):71211-71222.. View in PubMed
• Medulloblastoma initiation and spread: Where neurodevelopment, microenvironment and cancer cross pathways. J Neurosci Res. 2016 12; 94(12):1511-1519.. View in PubMed
• Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases. Int J Mol Sci. 2016 Sep 02; 17(9).. View in PubMed
• Monoamine oxidase A (MAO A) inhibitors decrease glioma progression. Oncotarget. 2016 Mar 22; 7(12):13842-53.. View in PubMed
• Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer. Sci Rep. 2016 Mar 07; 6:22762.. View in PubMed
• Primary Intraosseous Meningioma. Neurosurg Clin N Am. 2016 Apr; 27(2):189-93.. View in PubMed
• Therapeutic effect of TMZ-POH on human nasopharyngeal carcinoma depends on reactive oxygen species accumulation. Oncotarget. 2016 Jan 12; 7(2):1651-62.. View in PubMed
• Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15; 314(23):2535-43.. View in PubMed
• A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells. Cancer Lett. 2016 Feb 28; 371(2):240-50.. View in PubMed
• Effects of fusion and conservative treatment on disc degeneration and rates of subsequent surgery after thoracolumbar fracture. J Neurosurg Spine. 2016 Mar; 24(3):476-82.. View in PubMed
• Nanoparticle biointerfacing by platelet membrane cloaking. Nature. 2015 Oct 01; 526(7571):118-21.. View in PubMed
• Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. J Biomed Sci. 2015 Aug 19; 22:71.. View in PubMed
• A Conserved Glycan in the C2 Domain of HIV-1 Envelope Acts as a Molecular Switch to Control X4 Utilization by Clonal Variants with Identical V3 Loops. PLoS One. 2015; 10(6):e0128116.. View in PubMed
• Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis: technical note. J Neurosurg. 2015 Aug; 123(2):362-72.. View in PubMed
• Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy. Am J Cancer Res. 2015; 5(5):1580-93.. View in PubMed
• First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity. Vaccine. 2015 May 28; 33(23):2690-6.. View in PubMed
• Introduction. Neurooncology: update on therapeutic options. Neurosurg Focus. 2015 Mar; 38(3):E1.. View in PubMed
• Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus. 2015 Mar; 38(3):E12.. View in PubMed
• Use of ERC-1671 Vaccine in a Patient with Recurrent Glioblastoma Multiforme after Progression during Bevacizumab Therapy: First Published Report. Perm J. 2015; 19(2):41-6.. View in PubMed
• Effects of convection-enhanced delivery of bevacizumab on survival of glioma-bearing animals. Neurosurg Focus. 2015 Mar; 38(3):E8.. View in PubMed
• Stereotactic radiosurgery to the resection cavity for brain metastases: prognostic factors and outcomes. J Radiosurg SBRT. 2015; 3(3):179-186.. View in PubMed

• Lenz, Heinz-Josef
• Zlokovic, Berislav
• Chang, Eric
• Attenello, Frank
• Wiemels, Joseph
• Tran, David