David Ashley

Overview:

Dr. Ashley's primary research focus is laboratory based, investigating the role of immunotherapy as a novel approach to the treatment of tumors of the central nervous system (CNS). Since beginning his appointment at the faculty level at Duke in August of 1995 his activities have centered on two main areas of investigation. The first involves both in vivo and in vitro studies of the use of molecular therapeutics to target a CNS tumor associated antigen. The second area of interest comprises a detailed analysis of the role of TGF beta, a protein messenger produced by tumors of the CNS, both in the pathogenesis of disease and as a possible target for immunotherapy.

In addition to his laboratory role Dr. Ashley is involved in the design and application of a variety of clinical research protocols in the treatment of children with malignant brain tumors.

Positions:

Rory David Deutsch Distinguished Professor of Neuro-Oncology

Neurosurgery
School of Medicine

Professor of Neurosurgery

Neurosurgery
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in Pediatrics

Pediatrics, Neurology
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

F.R.A.C.P. 1993

Royal Australasian College of Physicians (Australia)

M.B.B.S. 1994

University of Melbourne (Australia)

Ph.D. 1998

University of Melbourne (Australia)

Grants:

LGG-14C03: A Phase III study comparing two carboplatin containing regimens for children and young adults with previously untreated low grade glioma

Administered By
Duke Cancer Institute
Awarded By
Ann & Robert H Lurie Children's Hospital of Chicago
Role
Principal Investigator
Start Date
End Date

SJMB12: A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma

Administered By
Pediatrics, Hematology-Oncology
Awarded By
St. Jude Children's Research Hospital
Role
Principal Investigator
Start Date
End Date

NEWLY DIAGNOSED CHILDREN (LESS THAN 10 YEARS OLD) WITH MEDULLOBLASTOMA AND OTHER CENTRAL NERVOUS SYSTEMPRIMITIVE NEURO-ECTODERMAL TUMORS:CLINICAL AND MOLECULAR RISK-TAILORED INTENSIVE AND COMPRESSED INDUCTION CHEMOTHERAPY FOLLOWED BY CONSOLIDATION WI

Administered By
Duke Cancer Institute
Awarded By
Research Institute at Nationwide Children's Hospital
Role
Principal Investigator
Start Date
End Date

Collaborative Network for Neuroooncology Clinical Trials (CONNECT)

Administered By
Duke Cancer Institute
Awarded By
Cincinnati Children's Hospital Medical Center
Role
Principal Investigator
Start Date
End Date

Publications:

Management of glioblastoma: State of the art and future directions.

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.
Authors
Tan, AC; Ashley, DM; López, GY; Malinzak, M; Friedman, HS; Khasraw, M
MLA Citation
Tan, Aaron C., et al. “Management of glioblastoma: State of the art and future directions.Ca Cancer J Clin, vol. 70, no. 4, July 2020, pp. 299–312. Pubmed, doi:10.3322/caac.21613.
URI
https://scholars.duke.edu/individual/pub1446606
PMID
32478924
Source
pubmed
Published In
Ca: a Cancer Journal for Clinicians
Volume
70
Published Date
Start Page
299
End Page
312
DOI
10.3322/caac.21613

The integrated genomic and epigenomic landscape of brainstem glioma.

Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. The majority of tumors within H3-Pons and-H3-Medulla harbors H3F3A mutations but shows distinct methylation patterns that correlate with anatomical localization within the pons or medulla, respectively. Clinical data show significantly different overall survival between these clusters, and pathway analysis demonstrates different oncogenic mechanisms in these samples. Our findings indicate that the integration of genetic and epigenetic data can facilitate better understanding of brainstem gliomagenesis and classification, and guide future studies for the development of novel treatments for this disease.
Authors
Chen, LH; Pan, C; Diplas, BH; Xu, C; Hansen, LJ; Wu, Y; Chen, X; Geng, Y; Sun, T; Sun, Y; Zhang, P; Wu, Z; Zhang, J; Li, D; Zhang, Y; Wu, W; Wang, Y; Li, G; Yang, J; Wang, X; Xu, C; Wang, S; Waitkus, MS; He, Y; McLendon, RE; Ashley, DM; Yan, H; Zhang, L
MLA Citation
Chen, Lee H., et al. “The integrated genomic and epigenomic landscape of brainstem glioma.Nat Commun, vol. 11, no. 1, June 2020, p. 3077. Pubmed, doi:10.1038/s41467-020-16682-y.
URI
https://scholars.duke.edu/individual/pub1447966
PMID
32555164
Source
pubmed
Published In
Nature Communications
Volume
11
Published Date
Start Page
3077
DOI
10.1038/s41467-020-16682-y

CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING - A COMPARATIVE OUTCOMES ANALYSIS

Authors
Finlay, J; Mynarek, M; Dhall, G; Lafay-Cousin, L; Mazewski, C; Ashley, D; Leary, S; von Bueren, A; Gerber, N; Cohen, B; Robinson, G; Geyer, JR; Tait, D; Stanek, J; Gajjar, A; Rutkowski, S
MLA Citation
Finlay, Jonathan, et al. “CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING - A COMPARATIVE OUTCOMES ANALYSIS.” Neuro Oncology, vol. 21, OXFORD UNIV PRESS INC, 2019, pp. 183–84.
URI
https://scholars.duke.edu/individual/pub1433005
Source
wos
Published In
Neuro Oncology
Volume
21
Published Date
Start Page
183
End Page
184

FATIGUE SYMPTOMS IN SURVIVORS OF CHILDHOOD CANCER: A COMPARISON OF PATIENT AND PARENT REPORT

Authors
McCarthy, MC; DeLuca, CR; Papachristos, D; Anderson, VA; Ashley, DM
MLA Citation
McCarthy, M. C., et al. “FATIGUE SYMPTOMS IN SURVIVORS OF CHILDHOOD CANCER: A COMPARISON OF PATIENT AND PARENT REPORT.” Neuro Oncology, vol. 12, no. 6, OXFORD UNIV PRESS INC, 2010, pp. II29–30.
URI
https://scholars.duke.edu/individual/pub1439479
Source
wos
Published In
Neuro Oncology
Volume
12
Published Date
Start Page
II29
End Page
II30

Pediatric brain tumor patients: their parents' perceptions of the hospital experience.

Studies have shown that admission to the hospital of a child can induce feelings of fear and helplessness in parents, challenging usual patterns of coping and parenting competence. Stress has been associated with parents' need to establish effective communication with staff and their need for information, ready access to their children, and participation in decision making relating to their child's care. This study of coping and adjustment was undertaken with the parents, including mothers and fathers, of children under 18 years of age diagnosed with a brain tumor, presenting at Royal Children's Hospital, Melbourne, between 2001 and 2002 (N=53). It was a prospective study using repeated measures over time. Participants in the study were involved in a questionnaire interview at 4 different points: at the time of diagnosis, 6 months postdiagnosis, 1 year postdiagnosis, and 2 years postdiagnosis, in which they were asked, among other things, about their experience of the hospital. The point of diagnosis was marked by a high level of dependence, with parents coping with rapid decision making and shock, and the surrender of care of their child. Parents identified high levels of information need but noted that they were often too stressed to take in information early on, and that this information need persisted up to the 2-year postdiagnosis point. More parents expressed dissatisfaction with the hospital and particularly with their interactions with the health care team at the 6-month post-diagnosis period, reflecting a possible reduction in attention given to families once they had settled into the treatment routine and the crisis of diagnosis had passed.
Authors
Jackson, AC; Stewart, H; O'Toole, M; Tokatlian, N; Enderby, K; Miller, J; Ashley, D
MLA Citation
Jackson, Alun C., et al. “Pediatric brain tumor patients: their parents' perceptions of the hospital experience.J Pediatr Oncol Nurs, vol. 24, no. 2, Mar. 2007, pp. 95–105. Pubmed, doi:10.1177/1043454206296030.
URI
https://scholars.duke.edu/individual/pub1439445
PMID
17332423
Source
pubmed
Published In
Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses
Volume
24
Published Date
Start Page
95
End Page
105
DOI
10.1177/1043454206296030