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Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.

ABSTRACT: Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated. Four of five of the patients had potential clinical benefit (partial response or stable disease greater than 6 months on therapy). We further describe the specific drug properties of each agent chosen and discuss characteristics relevant in their evaluation for therapeutic suitability. Finally, we summarize both tumor and drug characteristics that impact the ability to successfully incorporate targeted therapies into CNS malignancy management.

SUBMITTER: Marini BL

PROVIDER: S-EPMC5584679 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.

Marini Bernard L BL Benitez Lydia L LL Zureick Andrew H AH Salloum Ralph R Gauthier Angela C AC Brown Julia J Wu Yi-Mi YM Robinson Dan R DR Kumar Chandan C Lonigro Robert R Vats Pankaj P Cao Xuhong X Kasaian Katayoon K Anderson Bailey B Mullan Brendan B Chandler Benjamin B Linzey Joseph R JR Camelo-Piragua Sandra I SI Venneti Sriram S McKeever Paul E PE McFadden Kathryn A KA Lieberman Andrew P AP Brown Noah N Shao Lina L Leonard Marcia A S MAS Junck Larry L McKean Erin E Maher Cormac O CO Garton Hugh J L HJL Muraszko Karin M KM Hervey-Jumper Shawn S Mulcahy-Levy Jean M JM Green Adam A Hoffman Lindsey M LM Dorris Katie K Vitanza Nicholas A NA Wang Joanne J Schwartz Jonathan J Lulla Rishi R Smiley Natasha Pillay NP Bornhorst Miriam M Haas-Kogan Daphne A DA Robertson Patricia L PL Chinnaiyan Arul M AM Mody Rajen R Koschmann Carl C

Translational research : the journal of laboratory and clinical medicine 20170810

Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present th ...[more]

PMID: 28860053

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Project description:BackgroundPediatric brain tumors (PBT) stand as the leading cause of cancer-related deaths in children. Chemoradiation protocols have improved survival rates, even for non-resectable tumors. Nonetheless, radiation therapy carries the risk of numerous adverse effects that can have long-lasting, detrimental effects on the quality of life for survivors. The pursuit of chemotherapeutics that could obviate the need for radiotherapy remains ongoing. Several anti-tumor agents, including sunitinib, valproic acid, carboplatin, and panobinostat, have shown effectiveness in various malignancies but have not proven effective in treating PBT. The presence of the blood-brain barrier (BBB) plays a pivotal role in maintaining suboptimal concentrations of anti-cancer drugs in the central nervous system (CNS). Ongoing research aims to modulate the integrity of the BBB to attain clinically effective drug concentrations in the CNS. However, current findings on the interaction of exogenous chemical agents with the BBB remain limited and do not provide a comprehensive explanation for the ineffectiveness of established anti-cancer drugs in PBT.MethodsWe conducted our search for chemotherapeutic agents associated with the blood-brain barrier (BBB) using the following keywords: Chemotherapy in Cancer, Chemotherapy in Brain Cancer, Chemotherapy in PBT, BBB Inhibition of Drugs into CNS, Suboptimal Concentration of CNS Drugs, PBT Drugs and BBB, and Potential PBT Drugs. We reviewed each relevant article before compiling the information in our manuscript. For the generation of figures, we utilized BioRender software.FocusWe focused our article search on chemical agents for PBT and subsequently investigated the role of the BBB in this context. Our search criteria included clinical trials, both randomized and non-randomized studies, preclinical research, review articles, and research papers.FindingOur research suggests that, despite the availability of potent chemotherapeutic agents for several types of cancer, the effectiveness of these chemical agents in treating PBT has not been comprehensively explored. Additionally, there is a scarcity of studies examining the role of the BBB in the suboptimal outcomes of PBT treatment, despite the effectiveness of these drugs for other types of tumors.

Dataset Information

Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.

Publications

Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.

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