Transitioning to the next stage of leadership

POETIC RDMC UPDATE from Dr. Tanya Trippett

It has been an honor and a privilege to serve the children, families, doctors, nurses and pharmacists of the POETIC community, and our industry partners for 16 years. After 16 years of leadership as Director of POETIC, I believe that this is the perfect time to foster the development of POETIC’s next generation of leaders and visionaries. In so doing, I will transition from leadership as the Director of POETIC and will welcome Dr. Norman Lacayo of Stanford University as the next Director of POETIC on December 31, 2019. Dr. Lacayo brings to POETIC a strong foundation in pediatric oncology particularly in the areas of cancer genomics, leukemia and immunotherapy, all essential building blocks for advancement of the Mission of POETIC. I am confident that Dr. Lacayo will foster new vision and innovation in the establishment of precision-based approaches to cancer care for children with recurrent or refractory cancers. Under his direction, the horizon will be bright with hope for our nation’s children with cancer. Please join me in welcoming Dr. Norman Lacayo as Director of POETIC.

I look forward to focusing my efforts on international humanitarian initiatives to address disparities in cancer care for children in emerging nations.  We must not rest until all children have the same opportunity for cure of their cancer. Join us in ensuring that this Vision becomes a reality worldwide.

POETIC Making Headlines

Redefining ROI to “Return on Impact” Is His Lifelong Goal
Researchers make progress understanding a rare pediatric cancer
Vaccine innovation targets high-risk childhood cancers

Give Kids a Chance Act in the US House of Representatives

Past POETIC RDMC Newsletters

Papers

Gupta M, Kannappan S, Jain M, et al. Development and validation of a 21-gene prognostic signature in neuroblastoma. Sci Rep. 2023;13(1):12526. doi:10.1038/s41598-023-37714-9

Wang B, Li D, Cherkasova V, et al. Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis. Cancers (Basel). 2022;14(8):1908. doi:10.3390/cancers14081908

Reynolds CR, Tran S, Jain M, Narendran A. Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies. Vaccines (Basel). 2022;10(2):196. doi:10.3390/vaccines10020196

Grundy M, Narendran A. The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents. Front Pediatr. 2022;10:910268. doi:10.3389/fped.2022.910268

Jain M, Thakur S, Tran S, Zhang C, Sharma R, Anderson R, Nagashima Y and Narendran A. Lin28A oncogene governs stemness and metastatic potential in pediatric Neurocutaneous Melanosis – associated CNS tumors through let-7 independent mechanisms. Oncogene. Under Review ONC-2021-01913. June 2021.

Whiteside TL. Validation of plasma-derived small extracellular vesicles as cancer biomarkers. Nature Reviews Clinical Oncology. 2020;17(12):719-720. doi:10.1038/s41571-020-00433-5

Thakur S, Ruan Y, Zhang C, Lun X, Jayanthan A, Narendran A. Human SNF5 arming of double-deleted vaccinia virus shows oncolytic and cytostatic activity against central nervous system atypical teratoid/rhabdoid tumor cells. Cancer Gene Therapy. Published online July 17, 2020:1-6. doi:10.1038/s41417-020-0199-2

Hoshino A, Kim HS, Bojmar L, et al. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell. 2020;182(4):1044-1061.e18. doi:10.1016/j.cell.2020.07.009

Geoerger B, Zwaan CM, Marshall LV, et al. Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Lancet Oncol. 2020;21(1):134-144. doi:10.1016/S1470-2045(19)30693-X

Zhang H, Lyden D. Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization. Nat Protoc. 2019;14(4):1027-1053. doi:10.1038/s41596-019-0126-x

Swift L, Zhang C, Kovalchuk O, Boklan J, Trippett T, Narendran A. Dual functionality of the antimicrobial agent taurolidine which demonstrates effective anti-tumor properties in pediatric neuroblastoma. Invest New Drugs. July 2019. doi:10.1007/s10637-019-00816-1

Obaid H, Kannappan S, Gupta M, et al. In Vitro Investigation Demonstrates IGFR/VEGFR Receptor Cross Talk and Potential of Combined Inhibition in Pediatric Central Nervous System Atypical Teratoid Rhabdoid Tumors. Curr Cancer Drug Targets. November 2019. doi:10.2174/1568009619666191111153049

Jayanthan A, Hofmann B, Meier-Stephenson V, et al. Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. J Pediatr Hematol Oncol. 2019;41(6):e359-e370. doi:10.1097/MPH.0000000000001416

Brennan L, Narendran A. Cancer Stem Cells in the Development of Novel Therapeutics for Refractory Pediatric Leukemia. Stem Cells Dev. 2019;28(19):1277-1287. doi:10.1089/scd.2019.0035

Swift L, Jayanthan A, Ruan Y, et al. Targeting the Proteasome in Refractory Pediatric Leukemia Cells: Characterization of Effective Cytotoxicity of Carfilzomib. Target Oncol. 2018;13(6):779-793. doi:10.1007/s11523-018-0603-0

Manley PE, Trippett T, Smith AA, et al. A phase 1/2 dose-finding, safety, and activity study of cabazitaxel in pediatric patients with refractory solid tumors including tumors of the central nervous system. Pediatr Blood Cancer. 2018;65(9):e27217. doi:10.1002/pbc.27217

Macy ME, Kieran MW, Chi SN, et al. A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high-grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators’ Consortium study. Pediatr Blood Cancer. 2017;64(11). doi:10.1002/pbc.26621

Cooper TM, Sison EAR, Baker SD, et al. A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators’ Consortium study (POE 10-03). Pediatr Blood Cancer. 2017;64(8). doi:10.1002/pbc.26414

Pearson ADJ, Federico SM, Aerts I, et al. A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid tumors. Oncotarget. 2016;7(51):84736-84747. doi:10.18632/oncotarget.12450

Singh A, Ruan Y, Tippett T, Narendran A. Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015;34(1):104-104. doi:10.1186/s13046-015-0222-x

Ruan Y, Kovalchuk A, Jayanthan A, et al. Druggable targets in pediatric neurocutaneous melanocytosis: Molecular and drug sensitivity studies in xenograft and ex vivo tumor cell culture to identify agents for therapy. Neuro Oncol. 2015;17(6):822-831. doi:10.1093/neuonc/nou310

McKenzie BA, Zemp FJ, Pisklakova A, et al. In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells. Neuro Oncol. 2015;17(8):1086-1094. doi:10.1093/neuonc/nou359

Hoshino A, Costa-Silva B, Shen T-L, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329-335. doi:10.1038/nature15756

Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816-826. doi:10.1038/ncb3169

Thakur BK, Zhang H, Becker A, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Research. 2014;24(6):766-769. doi:10.1038/cr.2014.44

Spence T, Perotti C, Sin-Chan P, et al. A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in embryonal tumor with multilayered rosettes. Neuro Oncol. 2014;16(1):62-71. doi:10.1093/neuonc/not162

Jayanthan A, Ruan Y, Truong TH, Narendran A. Aurora kinases as druggable targets in pediatric leukemia: heterogeneity in target modulation activities and cytotoxicity by diverse novel therapeutic agents. PLoS One. 2014;9(7):e102741-e102741. doi:10.1371/journal.pone.0102741

Triscott J, Lee C, Foster C, et al. Personalizing the Treatment of Pediatric Medulloblastoma: Polo-like Kinase 1 as a Molecular Target in High-Risk Children. Cancer Res. 2013;73(22):6734. doi:10.1158/0008-5472.CAN-12-4331

Singh A, Lun X, Jayanthan A, et al. Profiling pathway-specific novel therapeutics in preclinical assessment for central nervous system atypical teratoid rhabdoid tumors (CNS ATRT): favorable activity of targeting EGFR- ErbB2 signaling with lapatinib. Mol Oncol. 2013;7(3):497-512. doi:10.1016/j.molonc.2013.01.001

Macy ME, Duncan T, Whitlock J, et al. A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors. Pediatr Blood Cancer. 2013;60(2):230-236. doi:10.1002/pbc.24278

Lun X, Ruan Y, Jayanthan A, et al. Double-deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors. Mol Oncol. 2013;7(5):944-954. doi:10.1016/j.molonc.2013.05.004

Jayanthan A, Cooper TM, Hoeksema KA, et al. Occurrence and modulation of therapeutic targets of Aurora kinase inhibition in pediatric acute leukemia cells. Leukemia & Lymphoma. 2013;54(7):1505-1516. doi:10.3109/10428194.2012.752079

Gore L, Trippett TM, Katzenstein HM, et al. A Multicenter, First-in-Pediatrics, Phase 1, Pharmacokinetic and Pharmacodynamic Study of Ridaforolimus in Patients with Refractory Solid Tumors. Clin Cancer Res. 2013;19(13):3649. doi:10.1158/1078-0432.CCR-12-3166

Lee C, Fotovati A, Triscott J, et al. Polo-Like Kinase 1 Inhibition Kills Glioblastoma Multiforme Brain Tumor Cells in Part Through Loss of SOX2 and Delays Tumor Progression in Mice. STEM CELLS. 2012;30(6):1064-1075. doi:10.1002/stem.1081

de Oliveira JC, Brassesco MS, Scrideli CA, Tone LG, Narendran A. MicroRNA expression and activity in pediatric acute lymphoblastic leukemia (ALL). Pediatric Blood & Cancer. 2012;59(4):599-604. doi:10.1002/pbc.24167

Banderali U, Jayanthan A, Hoeksema KA, Narendran A, Giles WR. Ion channels in pediatric CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT) cells: potential targets for novel therapeutic agents. Journal of Neuro-Oncology. 2012;107(1):111-119. doi:10.1007/s11060-011-0735-x

Abd Elmoneim A, Gore L, Ricklis RM, et al. Phase I dose-escalation trial of clofarabine followed by escalating doses of fractionated cyclophosphamide in children with relapsed or refractory acute leukemias. Pediatric Blood & Cancer. 2012;59(7):1252-1258. doi:10.1002/pbc.24264

Knipstein J, Gore L. Entinostat for treatment of solid tumors and hematologic malignancies. Expert Opinion on Investigational Drugs. 2011;20(10):1455-1467. doi:10.1517/13543784.2011.613822

Jayanthan A, Bernoux D, Bose P, Riabowol K, Narendran A. Multi-tyrosine kinase inhibitors in preclinical studies for pediatric CNS AT/RT: Evidence for synergy with Topoisomerase-I inhibition. Cancer Cell International. 2011;11(1):44. doi:10.1186/1475-2867-11-44

Hoeksema KA, Jayanthan A, Cooper T, et al. Systematic in-vitro evaluation of the NCI/NIH Developmental Therapeutics Program Approved Oncology Drug Set for the identification of a candidate drug repertoire for MLL-rearranged leukemia. Onco Targets Ther. 2011;4:149-168. doi:10.2147/OTT.S21553

Farrar JE, Vlachos A, Atsidaftos E, et al. Ribosomal protein gene deletions in Diamond-Blackfan anemia. Blood. 2011;118(26):6943-6951. doi:10.1182/blood-2011-08-375170

Chaponis D, Barnes JW, Dellagatta JL, et al. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for orthotopic malignant gliomas. J Neurooncol. 2011;104(1):179-189. doi:10.1007/s11060-010-0502-4

Birks DK, Barton VN, Donson AM, Handler MH, Vibhakar R, Foreman NK. Survey of MicroRNA expression in pediatric brain tumors. Pediatric Blood & Cancer. 2011;56(2):211-216. doi:10.1002/pbc.22723

Birks DK, Donson AM, Patel PR, et al. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival. Neuro Oncol. 2011;13(12):1296-1307. doi:10.1093/neuonc/nor140

Bagatell R, Herzog CE, Trippett TM, et al. Pharmacokinetically guided phase 1 trial of the IGF-1 receptor antagonist RG1507 in children with recurrent or refractory solid tumors. Clin Cancer Res. 2011;17(3):611-619. doi:10.1158/1078-0432.CCR-10-1731

Trippett TM, Herzog C, Whitlock JA, et al. Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: a study of the pediatric oncology experimental therapeutic investigators’ consortium. J Clin Oncol. 2009;27(30):5102-5108. doi:10.1200/JCO.2008.20.8975

Jayanthan A, Howard SC, Trippett T, et al. Targeting the Bcl-2 family of proteins in Hodgkin lymphoma: in vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737. Leuk Lymphoma. 2009;50(7):1174-1182. doi:10.1080/10428190902943069

Narendran A, Coppes L, Jayanthan A, et al. Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics. J Neurooncol. 2008;90(2):171-180. doi:10.1007/s11060-008-9653-y

Jayanthan A, Fowler J, Hawkins L, et al. Effects of Hsp90 inhibition in neuroblastoma: analysis of drug sensitivity, target modulation and the influence of bone marrow microenvironment. J Exp Ther Oncol. 2008;7(3):183-193. PMID: 19066127

Bagatell R, Gore L, Egorin MJ, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study. Clin Cancer Res. 2007;13(6):1783-1788. doi:10.1158/1078-0432.CCR-06-1892

Abstracts and Posters

Boklan J, Narendran A, Bielamowicz K, Trippett T, Brown V, DuBois s, Eshun F, Gelfond J, Zomet A, Lacayo N, Langevin AM. Abstract 1123: POE14-01: A phase I study of carfilzomib in combination with cyclophosphamide and etoposide for children, adolescents and young adults with relapsed/refractory leukemias or solid tumors. 55th Congress of the International Society of Paediatric Oncology (SIOP). October 11-14, 2023. Ottawa, ON.

Tran S, Sipila P, Zhang C, Maese L, Lacayo N, and Narendran A. A novel anti-cancer vaccine approach for the effective treatment of refractory leukemia in children. Panelist Poster Discussion Session: Novel Therapeutics and Targets. 55th Congress of the International Society of Paediatric Oncology (SIOP). October 11-14, 2023. Ottawa, ON.

Sharma R. Targeting CDK9 in KMT2A-Rearranged Infant Leukemia: Evidence for Activity and Drug Synergy with Enitociclib. In: ASH; 2023. Accessed November 8, 2023. https://ash.confex.com/ash/2023/webprogram/Paper180567.html

Tran S, Sipila P, Frigault MM, et al. Abstract 1558: Targeting CDK9 via the small-molecule inhibitor enitociclib as a therapeutic strategy to treat MYCN-amplified rhabdomyosarcoma and neuroblastoma in children. Cancer Research. 2023;83(7_Supplement):1558. doi:10.1158/1538-7445.AM2023-1558

Tran S, Thakur S, Jain M, Zhang C, Narendran A. Abstract 1121: Identification and in vivo validation of unique anti-oncogenic properties and mechanisms involving protein kinase signalling and autophagy mediated by the investigational new agent PV-10. Cancer Research. 2022;82(12_Supplement):1121. doi:10.1158/1538-7445.AM2022-1121

Sharma R, Zhang C, Maese LD, Lacayo NJ, Narendran A. Menin inhibitors as targeted therapeutics in KMT2a rearranged infant leukemia and the identification of effective treatment combinations. JCO. 2022;40(16_suppl):10024-10024. doi:10.1200/JCO.2022.40.16_suppl.10024

Sharma R, Thakur S, Jain M, Zhang C, Langevin AM, Narendran A. Preclinical evaluation of the ETS inhibitor TK216 against relapsed and refractory childhood leukemia. JCO. 2021;39(15_suppl):10033-10033. doi:10.1200/JCO.2021.39.15_suppl.10033

Satbir T, Tran S, Jain M, et al. A Novel Anti-Cancer Vaccine Approach for the Treatment of High-Risk Leukemia in Children. Blood. 2020;136(Supplement 1):25-25. doi:10.1182/blood-2020-143381

Zhang C, Sharma R, Satbir T, et al. Establishing a Novel in Vitro Informed Precision Clinical Trial Pathway for Refractory Pediatric Leukemia. Blood. 2019;134(Supplement_1):2633-2633. doi:10.1182/blood-2019-131444

Trippett T, Berger M, Lyden D, et al. Characterization of the Genetic Landscape of Low Mutation Burden Malignancies through Multi-Parallel Genomic and Immunologic Analysis. 2018.

Trippett T, Simko S, Ye C, Caron H, Georger B. Imatrixcobi: a phase I/II, dose-escalation study of the safety, pharmacokinetics, and preliminary efficacy of cobimetinib in paediatric and young adult patients with refractory/relapsed tumor. 2016.

Kieran MW, Yao X, Macy M, et al. Final Results of a Prospective Multi-Institutional Phase II study of Everolimus (RAD001), an MTOR Inhibitor, in Pediatric Patients with Recurrent or Progressive Low-Grade Glioma. A POEITC Consortium Trial. Neuro Oncol. 2014;16(Suppl 3):iii27-iii27. doi:10.1093/neuonc/nou208.15

Trippett T, Smith A, Neville K, et al. Phase I/II trial of vorinostat in combination with etoposide in pediatric patients with relapsed/refractory solid tumors; Abstract # B81. 2013.

Pearson A, Federico S, Aerts I, et al. A phase I study of ridaforolimus (MK-8669) in pediatric patients with advanced solid tumors; Abstract # 10027. 2013.

Macy M, Kieran M, Chi S, et al. A phase II trial of radiation and cetuximab followed by irinotecan/cetuximab for children with newly diagnosed diffuse pontine tumors and high-grade astrocytomas; Abstract # 10030. 2013.

Hagerty M, Jayanthan A, Ruan Y, Trippett T, Narendran A. Effective targeting of PI3K/mTOR pathways with GDC-0980 in FLT-3 mutant pediatric leukemia; Abstract # C175. 2013.

Gore L, Trippett T, Katzenstein H, et al. multicenter, first-in-pediatric patients phase I study of ridaforolimus (AP23573, MK-8669) in patients (pts) with refractory solid tumors; Abstract # 48828. In: ; 2010.

Bagatell R, Herzog C, Trippett T, et al. Pharmacokinetically (PK) Guided Phase 1 Trial of the IGF-1 Receptor Antagonist R1507 Administered Weekly in Children with Recurrent or Refractory Solid Tumors; Abstract# 21200. 2009.

Jayanthan A, Howard S, Trippett T, et al. Targeting the Bcl-2 family of protein in Hodgkin Lymphoma: In vitro cytotoxicity, target modulation, and drug combination studies of the BH3 mimetic ABT-373. In: Abstract # 3626; 2008.

Trippett TM, Kuttesch J, Herzog C, et al. A phase I study of cetuximab and irinotecan in pediatric patients (pts) with refractory solid tumors. JCO. 2007;25(18_suppl):9547-9547. doi:10.1200/jco.2007.25.18_suppl.9547

Narendran A, Gore L, Bagatell R, et al. An Experimental Model for Target Modulation Analysis in Early Clinical Trials: Effects on Hsp90 Client Proteins in Cells of Patients Treated with 17-AAG. Vol 48.; 2007.

Gore L, Kuttesch J, Hunger SP, et al. A phase Ib study of oxaliplatin in combination with fluorouracil (5FU) and leucovorin (LV) in pediatric patients (pts) with advanced solid tumors. JCO. 2007;25(18_suppl):9548-9548. doi:10.1200/jco.2007.25.18_suppl.9548

Reviews

Mobahat M, Narendran A, Riabowol K. Survivin as a preferential target for cancer therapy. Int J Mol Sci. 2014;15(2):2494-2516. doi:10.3390/ijms15022494

Brabletz T, Lyden D, Steeg PS, Werb Z. Roadblocks to translational advances on metastasis research. Nat Med. 2013;19(9):1104-1109. doi:10.1038/nm.3327

August KJ, Narendran A, Neville KA. Pediatric Relapsed or Refractory Leukemia: New Pharmacotherapeutic Developments and Future Directions. Drugs. 2013;73(5):439-461. doi:10.1007/s40265-013-0026-2

Neville KA, Becker ML, Goldman JL, Kearns GL. Developmental pharmacogenomics. Pediatric Anesthesia. 2011;21(3):255-265. doi:10.1111/j.1460-9592.2011.03533.x

Gore L, Trippett TM. Emerging Non-transplant-based Strategies in Treating Pediatric Non-Hodgkin’s Lymphoma. Curr Hematol Malig Rep. 2010;5(4):177-184. doi:10.1007/s11899-010-0058-6

Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nature Reviews Cancer. 2009;9(4):285-293. doi:10.1038/nrc2621

Book chapters

Lamers F, Narendran A. Pathways of Intrinsic Apoptosis in Neuroblastoma: Targets for Therapeutics and New Drug Development | IntechOpen. In: Neuroblastoma; 2013. https://www.intechopen.com/books/neuroblastoma/pathways-of-intrinsic-apoptosis-in-neuroblastoma-targets-for-therapeutics-and-new-drug-development.

Narendran A, Leung A, Ho J. Influence and Implications of Nutrition and Metabolic Factors on the Growth and Survival of Pediatric Cancer Cells: The IGF Connection. In: Obesity and Cancer Research. Nova Science Publishers, Hauppauge NY; 2009.

Books

Lyden D, Welch DR, Psaila B. Cancer Metastasis: Biologic Basis and Therapeutics. Cambridge University Press; 2011. https://books.google.com/books?id=4Ds8C0yTMzoC.