The Neurosurgical Oncology Unit aims to develop novel therapeutics for Glioblastoma (GBM)–the most common primary malignant CNS. Despite aggressive management with maximal surgical resection, radiation, and chemotherapy, median and 5-year survival rates remain low (15 months and 5.6%, respectively). Tumor-specific contributors to treatment failure include cellular and genetic heterogeneity and a highly immunosuppressive tumor microenvironment. GBMs also harbor self-renewing, tumorigenic glioma stem-like cells (GSCs) that contribute to tumor initiation, maintenance, and recurrence. The need for novel GBM therapeutic strategies is urgent.
The role of primary cilia in cancer has garnered attention over the last decade and provides opportunities for the development of novel therapeutic strategies. Primary cilia are non-motile, highly conserved microtubule-based organelles that project from the cytoplasmic membrane in a single copy from virtually all mammalian cells. The organelle is required for several key signal transduction cascades implicated in cancer. While GBM cells show aberrant ciliogenesis and downregulation of cilia-related genes, functional, mature primary cilia are present in GBM cell lines and biopsies (Figure 1).
Investigations into the functional significance of primary cilia in GBM tumorigenesis is in a nascent stage. A deeper understanding of the specific signaling cascades and mechanisms regulating ciliogenesis in GBM and their impact on proliferation, invasion, treatment resistance, and immunosuppression is critical to moving the field forward and developing a potentially new paradigm of effective, “cilia-centric” therapeutic strategies. This is the overarching aim of our group.
Lab Members:
- Desmond A. Brown, M.D., Ph.D., Assistant Clinical Investigator, Head of Neurosurgical Oncology Unit
- Masahiro Oishi, M.D., Ph.D., Research Fellow
- Mi-Yeon Jung, M.D., Biologist
- Afia Agyeman-Andoh, NIH-Pre-Doc IRTA
Selected Publications
2022
Letchuman V, Ampie L, Shah AH, Brown DA, Heiss JD, Chittiboina P (2022)
Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes.
Neurosurg Focus, 52:E5. PubMed ID: 35104794
Brown DA, Goyal A, Richter KR, Haglin JM, Himes BT, Lu VM, Snyder K, Hughes J, Decker PA, Opoku-Darko M, Link MJ, Burns TC, Parney IF (2022)
Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.
J Neurosurg, 136:30-39. PubMed ID: 34214988
Vivas-Buitrago T, Domingo RA, Tripathi S, De Biase G, Brown D, Akinduro OO, Ramos-Fresnedo A, Sabsevitz DS, Bendok BR, Sherman W, Parney IF, Jentoft ME, Middlebrooks EH, Meyer FB, Chaichana KL, Quinones-Hinojosa A (2022)
Influence of supramarginal resection on survival outcomes after gross-total resection of IDH-wild-type glioblastoma.
J Neurosurg, 136:1-8. PubMed ID: 34087795
2021
Himes BT, Geiger PA, Ayasoufi K, Bhargav AG, Brown DA, Parney IF (2021)
Immunosuppression in Glioblastoma: Current Understanding and Therapeutic Implications.
Front Oncol, 11:770561. PubMed ID: 34778089
Renfrow JJ, Julian BQ, Brown DA, Tatter SB, Laxton AW, Lesser GJ, Strowd RE, Parney IF (2021)
A Review on the Surgical Management of Insular Gliomas.
Can J Neurol Sci,:1-9. PubMed ID: 34711299
Brown DA, Goyal A, Richter KR, Haglin JM, Himes BT, Lu VM, Snyder K, Hughes J, Decker PA, Opoku-Darko M, Link MJ, Burns TC, Parney IF (2022)
Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.
J Neurosurg, 136:30-39. PubMed ID: 34214988
Munoz-Casabella A, Alvi MA, Rahman M, Burns TC, Brown DA (2021)
Laser Interstitial Thermal Therapy for Recurrent Glioblastoma: Pooled Analyses of Available Literature.
World Neurosurg, 153:91-97.e1. PubMed ID: 34087459
2020
Brown DA, Goyal A, Kerezoudis P, Alvi MA, Himes BT, Bydon M, Van Gompel JJ, Chaichana KL, Quiñones-Hinojosa A, Burns TC, Yan E, Parney IF (2020)
Adjuvant radiation for WHO grade II and III intracranial meningiomas: insights on survival and practice patterns from a National Cancer Registry.
J Neurooncol, 149:293-303. PubMed ID: 32860156
Brown DA, Goyal A, Kerezoudis P, Alvi MA, Himes BT, Bydon M, Van Gompel JJ, Chaichana KL, Quiñones-Hinojosa A, Burns TC, Yan E, Parney IF (2020)
Adjuvant radiation for WHO grade II and III intracranial meningiomas: insights on survival and practice patterns from a National Cancer Registry.
J Neurooncol, 149:293-303. PubMed ID: 32860156
Brown DA, Goyal A, Takami H, Graffeo CS, Mahajan A, Krauss WE, Bydon M (2020)
Radiotherapy in addition to surgical resection may not improve overall survival in WHO grade II spinal ependymomas.
Clin Neurol Neurosurg, 189:105632. PubMed ID: 31862631
Brown DA, Lu VM, Himes BT, Burns TC, Quiñones-Hinojosa A, Chaichana KL, Parney IF (2020)
Breast brain metastases are associated with increased risk of leptomeningeal disease after stereotactic radiosurgery: a systematic review and meta-analysis.
Clin Exp Metastasis, 37:341-352. PubMed ID: 31950392
Brown DA, Hanalioglu S, Chaichana K, Duffau H (2020)
Transcorticosubcortical Approach for Left Posterior Mediobasal Temporal Region Gliomas: A Case Series and Anatomic Review of Relevant White Matter Tracts.
World Neurosurg, 139:e737-e747. PubMed ID: 32360919
Himes BT, Arnett AL, Merrell KW, Gates MJ, Bhargav AG, Raghunathan A, Brown DA, Burns TC, Parney IF (2020)
Glioblastoma Recurrence Versus Treatment Effect in a Pathology-Documented Series.
Can J Neurol Sci, 47:525-530. PubMed ID: 32077389
2019
Goyal A, Yolcu YU, Goyal A, Kerezoudis P, Brown DA, Graffeo CS, Goncalves S, Burns TC, Parney IF (2019)
The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance.
Neurosurg Focus, 47:E13. PubMed ID: 31786548
Lu VM, Kerezoudis P, Brown DA, Burns TC, Quinones-Hinojosa A, Chaichana KL (2019)
Hypofractionated versus standard radiation therapy in combination with temozolomide for glioblastoma in the elderly: a meta-analysis.
J Neurooncol, 143:177-185. PubMed ID: 30919157
Navarro-Bonnet J, Suarez-Meade P, Brown DA, Chaichana KL, Quinones-Hinojosa A (2019)
Following the light in glioma surgery: a comparison of sodium fluorescein and 5-aminolevulinic acid as surgical adjuncts in glioma resection.
J Neurosurg Sci, 63:633-647. PubMed ID: 31961116
Rinaldo L, Brown DA, Bhargav AG, Rusheen AE, Naylor RM, Gilder HE, Monie DD, Youssef SJ, Parney IF (2019)
Venous thromboembolic events in patients undergoing craniotomy for tumor resection: incidence, predictors, and review of literature.
J Neurosurg, 132:10-21. PubMed ID: 30611138
2018
Brown DA, Himes BT, Kerezoudis P, Chilinda-Salter YM, Grewal SS, Spear JA, Bydon M, Burns TC, Parney IF (2018)
Insurance correlates with improved access to care and outcome among glioblastoma patients.
Neuro Oncol, 20:1374-1382. PubMed ID: 29893906