The Pediatric Preclinical Consortium (PPTC)

 

Development of new therapies for children with cancer presents unique challenges. Firstly, the incidence of cancer in children is relatively low; in the United States about 12,400 new cases are diagnosed annually in patients under 20 years old. Each year in Texas, almost 1,200 children and adolescents younger than 20 years of age are diagnosed with cancer, representing 10% of all cancers diagnosed in the U.S. Approximately 200 children and adolescents die of cancer each year, making cancer the most common cause of disease-related mortality for Texans 0-19 years of age.

Nationally, the overall cure rate for all childhood cancers is approaching seventy percent, and in many patients that ultimately fail curative therapy, initial responses to current multimodality treatments (surgery, radiation therapy and chemotherapy) are good, with overall 5-year Event-Free Survival approaching 80%. However, current approaches to curative therapy result in significant morbidity and long- term sequelae, including cardiac dysfunction and cognitive impairment. Further, dose-intensive chemotherapy with conventional agents has not significantly improved outcomes for patients that present with advanced or metastatic disease. The distribution of cancers in U.S. children is shown below. Foe rare tumors such as Ewing sarcoma, there are about 250 children diagnosed per year. As a consequence, relatively few trials of experimental agents are possible in these rare tumors.

 


 

The Pediatric Preclinical Testing Program (PPTP)

This was a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models. The PPTP was supported through an NCI research contract and testing occurred both at sites in the U.S and Australia (leukemias) that had expertise in specific childhood cancers.

The primary goal of the PPTP was to identify new agents that have the potential for significant activity when clinically evaluated against selected childhood cancers.

The program is based on a substantial body of data showing that appropriate childhood cancer preclinical in vivo models can recapitulate the anti-tumor activity of known effective agents and can prospectively identify novel agents subsequently shown to have clinical activity against specific cancers of children and adolescents. By facilitating development of a more reliable pediatric new agent prioritization process, the PPTP has contributed to the goal of identifying more effective treatments for children with cancer.

 

 

The PPTP developed standardized metrics to assess drug response, and presentation of large in vivo data sets. For each drug between 2 and 55 models of childhood cancer were used to assess broad-spectrum or tumor type activity. Over 100 models have been characterized with respect to exome sequencing, expression profiling and SNP analysis. Thus, a molecular data base is available to identify biomarkers of response to a specific agent.

Two graphic representations of data sets have been developed based upon tumor growth inhibition and tumor regression. The Heatmap format is shown below (A), with colors representing median group analysis for different levels of activity, shown on the right side (B).


The second format is modeled after the NCI COMPARE presentation used to graphically illustrate sensitivity of cell lines to a particular agent. The PPTP used this presentation to represent detailed response data for an individual drug.

The objective response results for both solid tumor and leukemia models are represented using a ‘COMPARE’ format, based on the objective response scoring criteria centered around the midpoint score of 0 that represents stable disease.


Activity of the MDM2 inhibitor RG7112. In the figure, xenografts with PD2 are indicated by a score of -3, and xenografts with regression (PR or CR) are indicated by bars to the right of the midpoint line. Red bars indicate xenografts with significant differences in EFS distribution between the treated and control groups. Xenograft models are shown on the left axis. Most antitumor activity was limited to acute lymphoblastic leukemia (ALL) xenograft models.

Methods, tumor demographics, poster presentations and COMPARE results can be obtained at: http://Greehey CCRI.UT Health San Antonio.edu/pptp/

The PPTC builds upon 10 years testing of novel agents against panels of cell lines in vitro and tumor xenografts models in mice that represent childhood solid tumors, brain tumors and acute lymphoblastic leukemias. Over 80 drugs or drug combinations have been tested in 83 xenograft models of childhood cancer (kidney cancers, sarcomas, neuroblastoma, brain cancers and acute lymphoblastic leukemia). These studies have identified novel drugs and drug combinations that are now in clinical trial.

The PPTC is funded through UO1CA199297 from July 2015. The major changes from the PPTP will be a focus on combination drug testing that is based upon either genetic characteristics of particular childhood cancer models, or based upon observed responses to cytotoxic or molecularly targeted agents identified in the PPTP screen.

 

Bioluminescence imaging enhances analysis of drug responses in a patient-derived xenograft model of pediatric ALL. Jones L, Richmond J, Evans K, Carol H, Jing D, Kurmasheva RT, Billups CA, Houghton PJ, Smith MA, Lock RB. Clin Cancer Res. 2017 Jan 24. pii: clincanres.2392.2016. doi: 10.1158/1078-0432.CCR-16-2392. [Epub ahead of print] PMID:28119366

A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Jones L, Carol H, Evans K, Richmond J, Houghton PJ, Smith MA, Lock RB. Leukemia. 2016 Nov;30(11):2133-2141. doi: 10.1038/leu.2016.192. Epub 2016 Jul 15. Review. PMID:27416986

Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. Kurmasheva RT, Gorlick R, Kolb EA, Keir ST, Maris JM, Lock RB, Carol H, Kang M, Reynolds CP, Wu J, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2017 Apr;64(4). doi: 10.1002/pbc.26304. Epub 2016 Oct 27. PMID:27786412

Initial testing (stage 1) of the curaxin CBL0137 by the pediatric preclinical testing program. Lock R, Carol H, Maris JM, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Keir ST, Wu J, Purmal A, Gudkov A, Kurmashev D, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2017 Apr;64(4). doi: 10.1002/pbc.26263. Epub 2016 Sep 21. PMID:27650817

Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. Kurmasheva RT, Sammons M, Favours E, Wu J, Kurmashev D, Cosmopoulos K, Keilhack H, Klaus CR, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2017 Mar;64(3). doi: 10.1002/pbc.26218. Epub 2016 Aug 24. PMID:27555605

Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Murphy B, Yin H, Maris JM, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Keir ST, Kurmasheva RT, Dvorchik I, Wu J, Billups CA, Boateng N, Smith MA, Lock RB, Houghton PJ. Cancer Res. 2016 Oct 1;76(19):5798-5809. Epub 2016 Aug 5. PMID:27496711

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia. Khaw SL, Suryani S, Evans K, Richmond J, Robbins A, Kurmasheva RT, Billups CA, Erickson SW, Guo Y, Houghton PJ, Smith MA, Carol H, Roberts AW, Huang DC, Lock RB. Blood. 2016 Sep 8;128(10):1382-95. doi: 10.1182/blood-2016-03-707414. Epub 2016 Jun 24. PMID:27343252

Acute Sensitivity of Ph-like Acute Lymphoblastic Leukemia to the SMAC-Mimetic Birinapant. Richmond J, Robbins A, Evans K, Beck D, Kurmasheva RT, Billups CA, Carol H, Heatley S, Sutton R, Marshall GM, White D, Pimanda J, Houghton PJ, Smith MA, Lock RB. Cancer Res. 2016 Aug 1;76(15):4579-91. doi: 10.1158/0008-5472.CAN-16-0523. Epub 2016 Jun 14. PMID:27302164

Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program.Kang MH, Reynolds CP, Kolb EA, Gorlick R, Carol H, Lock R, Keir ST, Maris JM, Wu J, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2016 Oct;63(10):1744-52. doi: 10.1002/pbc.26064. Epub 2016 May 30. PMID:27238606

Identifying novel therapeutic agents using xenograft models of pediatric cancer. Kurmasheva RT, Houghton PJ. Cancer Chemother Pharmacol. 2016 Aug;78(2):221-32. doi: 10.1007/s00280-016-3042-6. Epub 2016 May 18. Review. PMID:27193096

Synergism of FAK and tyrosine kinase inhibition in Ph+ B-ALL. Churchman ML, Evans K, Richmond J, Robbins A, Jones L, Shapiro IM, Pachter JA, Weaver DT, Houghton PJ, Smith MA, Lock RB, Mullighan CG. JCI Insight. 2016;1(4). pii: e86082. Epub 2016 Apr 7. MID:27123491

Quantitative phosphotyrosine profiling of patient-derived xenografts identifies therapeutic targets in pediatric leukemia. Dolai S, Sia KC, Robbins AK, Zhong L, Heatley SL, Vincent TL, Hochgräfe F, Sutton R, Kurmasheva RT, Revesz T, White DL, Houghton PJ, Smith MA, Teachey DT, Daly RJ, Raftery MJ, Lock RB. Cancer Res. 2016 Mar 9. pii: canres.2786.2015. [Epub ahead of print] PMID:26960974

Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program. Gorlick R, Kolb EA, Keir ST, Maris JM, Lock RB, Carol H, Reynolds CP, Kang MH, Billups CA, Collins J, Kurmashev D, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2016 Mar;63(3):443-50. doi: 10.1002/pbc.25826. Epub 2015 Nov 24.PMID:26797892

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. Attiyeh EF, Maris JM, Lock R, Reynolds CP, Kang MH, Carol H, Gorlick R, Kolb EA, Keir ST, Wu J, Landesman Y, Shacham S, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2016 Feb;63(2):276-86. doi: 10.1002/pbc.25727. Epub 2015 Sep 23. PMID:26398108

Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation. Geier B, Kurmashev D, Kurmasheva RT, Houghton PJ. Front Oncol. 2015 Aug 26;5:193. doi: 10.3389/fonc.2015.00193. eCollection 2015. Review. PMID:26380223

Initial testing (stage 1) of the anti-microtubule agents cabazitaxel and docetaxel, by the pediatric preclinical testing program. Reynolds CP, Kang MH, Maris JM, Kolb EA, Gorlick R, Wu J, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2015 Jul 7. doi: 10.1002/pbc.25611. PMID: 26154614

AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. Moradi Manesh D, El-Hoss J, Evans K, Richmond J, Toscan CE, Bracken LS, Hedrick A, Sutton R, Marshall GM, Wilson WR, Kurmasheva RT, Billups C, Houghton PJ, Smith MA, Carol H, Lock RB. Blood. 2015 Jun 26. pii: blood-2014-12-618900. PMID: 26116659

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton PJ, Kurmasheva RT, Kolb EA, Gorlick R, Maris JM, Wu J, Tong Z, Arnold MA, Chatterjee M, Williams TM, Smith MA. Pediatr Blood Cancer. 2015 Jul;62(7):1214-21. doi: 10.1002/pbc.25474. PMID: 25809532

Effective targeting of the P53-MDM2 axis in preclinical models of infant MLL-rearranged acute lymphoblastic leukemia. Richmond J, Carol H, Evans K, High L, Mendomo A, Robbins A, Meyer C, Venn NC, Marschalek R, Henderson M, Sutton R, Kurmasheva RT, Kees UR, Houghton PJ, Smith MA, Lock RB. Clin Cancer Res. 2015 Mar 15;21(6):1395-405. PMID: 25573381

Evaluation of the in vitro and in vivo efficacy of the JAK inhibitor AZD1480 against JAK-mutated acute lymphoblastic leukemia. Suryani S, Bracken LS, Harvey RC, Sia KC, Carol H, Chen IM, Evans K, Dietrich PA, Roberts KG, Kurmasheva RT, Billups CA, Mullighan CG, Willman CL, Loh ML, Hunger SP, Houghton PJ, Smith MA, Lock RB. Mol Cancer Ther. 2015 Feb;14(2):364-74. PMID: 25504635

Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program. Smith MA, Reynolds CP, Kang MH, Kolb EA, Gorlick R, Carol H, Lock RB, Keir ST, Maris JM, Billups CA, Lyalin D, Kurmasheva RT, Houghton PJ. Clin Cancer Res. 2015 Feb 15;21(4):819-32. PMID: 25500058

Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program. Kolb EA, Gorlick R, Keir ST, Maris JM, Kang MH, Reynolds CP, Lock RB, Carol H, Wu J, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2015 Jun;62(6):1106-9. PMID: 25407467

Initial testing (stage 1) of the PARP inhibitor BMN 673 by the pediatric preclinical testing program: PALB2 mutation predicts exceptional in vivo response to BMN 673. Smith MA, Hampton OA, Reynolds CP, Kang MH, Maris JM, Gorlick R, Kolb EA, Lock R, Carol H, Keir ST, Wu J, Kurmasheva RT, Wheeler DA, Houghton PJ. Pediatr Blood Cancer. 2015 Jan;62(1):91-8. PMID: 25263539

Initial solid tumor testing (stage 1) of AZD1480, an inhibitor of Janus kinases 1 and 2 by the pediatric preclinical testing program. Houghton PJ, Kurmasheva RT, Lyalin D, Maris JM, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2014 Nov;61(11):1972-9. PMID: 25131802

Initial testing (stage 1) of glembatumumab vedotin (CDX-011) by the pediatric preclinical testing program. Kolb EA, Gorlick R, Billups CA, Hawthorne T, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2014 Oct;61(10):1816-21. PMID: 24912408

Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program. Carol H, Maris JM, Kang MH, Reynolds CP, Kolb EA, Gorlick R, Keir ST, Wu J, Kurmasheva RT, Houghton PJ, Smith MA, Lock RB, Lyalin D. Pediatr Blood Cancer. 2014 Aug;61(8):1493-6.. Erratum in: Pediatr Blood Cancer. 2014 Sep;61(9):1716. Lyalin, Dmitry [added].PMID: 24664981

Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program. Kang MH, Reynolds CP, Maris JM, Gorlick R, Kolb EA, Lock R, Carol H, Keir ST, Wu J, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2014 Aug;61(8):1486-9.PMID: 24623675

Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program. Kurmasheva RT, Reynolds CP, Kang MH, Allievi C, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2014 May;61(5):922-4. PMID: 24166988

Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program. Carol H, Gorlick R, Kolb EA, Morton CL, Manesh DM, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak A, Hickson I, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA, Lock R. Pediatr Blood Cancer. 2014 Feb;61(2):245-52. PMID: 24038993

Initial testing (Stage 1) of TAK-701, a humanized hepatocyte growth factor binding antibody, by the Pediatric Preclinical Testing Program. Houghton PJ, Kurmasheva RT, Kolb EA, Wu J, Gorlick R, Maris JM, Smith MA. Pediatr Blood Cancer. 2014 Feb;61(2):380-2. PMID: 24019233

Initial testing (stage 1) of the Polo-like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program. Gorlick R, Kolb EA, Keir ST, Maris JM, Reynolds CP, Kang MH, Carol H, Lock R, Billups CA, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2014 Jan;61(1):158-64. PMID: 23956067

Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program. Wood AC, Maris JM, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Wu J, Kurmasheva RT, Whiteman K, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2013 Nov;60(11):1860-7. PMID: 23798344

Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program. Kolb EA, Gorlick R, Reynolds CP, Kang MH, Carol H, Lock R, Keir ST, Maris JM, Billups CA, Desjardins C, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2013 Aug;60(8):1325-32. PMID: 23553917

The anti-CD19 antibody-drug conjugate SAR3419 prevents hematolymphoid relapse postinduction therapy in preclinical models of pediatric acute lymphoblastic leukemia. Carol H, Szymanska B, Evans K, Boehm I, Houghton PJ, Smith MA, Lock RB. Clin Cancer Res. 2013 Apr 1;19(7):1795-805. Erratum in: Clin Cancer Res. 2013 Jun 1;19(11):3108.PMID

Initial testing (stage 1) of temozolomide by the pediatric preclinical testing program. Keir ST, Maris JM, Reynolds CP, Kang MH, Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Wu J, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2013 May;60(5):783-90. PMID: 23335050

Initial testing (stage 1) of ganetespib, an Hsp90 inhibitor, by the Pediatric Preclinical Testing Program. Lock RB, Carol H, Maris JM, Kang MH, Reynolds CP, Kolb EA, Gorlick R, Keir ST, Billups CA, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2013 Jul;60(7):E42-5. PMID: 23303741

Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program. Reynolds CP, Kang MH, Carol H, Lock R, Gorlick R, Kolb EA, Kurmasheva RT, Keir ST, Maris JM, Billups CA, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2013 May;60(5):791-8.PMID: 23002019

Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program. Carol H, Reynolds CP, Kang MH, Keir ST, Maris JM, Gorlick R, Kolb EA, Billups CA, Geier B, Kurmasheva RT, Houghton PJ, Smith MA, Lock RB. Pediatr Blood Cancer. 2013 Apr;60(4):633-41. PMID:

Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program. Gorlick R, Kolb EA, Houghton PJ, Morton CL, Neale G, Keir ST, Carol H, Lock R, Phelps D, Kang MH, Reynolds CP, Maris JM, Billups C, Smith MA. Pediatr Blood Cancer. 2012 Dec 15;59(7):1266-74. PMID: 22315240

Evaluation of arsenic trioxide by the pediatric preclinical testing program with a focus on Ewing sarcoma. Smith MA, Kang MH, Reynolds CP, Kurmasheva RT, Alexander D, Billups CA, Toretsky JA, Houghton PJ. Pediatr Blood Cancer. 2012 Oct;59(4):753-5. PMID: 22315235

Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program. Keir ST, Morton CL, Wu J, Kurmasheva RT, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2012 Sep;59(3):586-8. PMID: 22190407

Testing of the Akt/PKB inhibitor MK-2206 by the Pediatric Preclinical Testing Program. Gorlick R, Maris JM, Houghton PJ, Lock R, Carol H, Kurmasheva RT, Kolb EA, Keir ST, Reynolds CP, Kang MH, Billups CA, Smith MA. Pediatr Blood Cancer. 2012 Sep;59(3):518-24 PMID: 22102563

Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. Batra V, Maris JM, Kang MH, Reynolds CP, Houghton PJ, Alexander D, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Billups CA, Smith MA. Pediatr Blood Cancer. 2012 Oct;59(4):749-52. PMID: 22052829

Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. Kolb EA, Gorlick R, Keir ST, Maris JM, Lock R, Carol H, Kurmasheva RT, Reynolds CP, Kang MH, Wu J, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2012 May;58(5):815-8. PMID: 22052798

Initial testing of the investigational NEDD8-activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program. Smith MA, Maris JM, Gorlick R, Kolb EA, Lock R, Carol H, Keir ST, Reynolds CP, Kang MH, Morton CL, Wu J, Smith PG, Yu J, Houghton PJ. Pediatr Blood Cancer. 2012 Aug;59(2):246-53. Erratum in: Pediatr Blood Cancer. 2012 Oct;59(4):772.PMID:

Initial testing of JNJ-26854165 (Serdemetan) by the pediatric preclinical testing program. Smith MA, Gorlick R, Kolb EA, Lock R, Carol H, Maris JM, Keir ST, Morton CL, Reynolds CP, Kang MH, Arts J, Bashir T, Janicot M, Kurmasheva RT, Houghton PJ. Pediatr Blood Cancer. 2012 Aug;59(2):329-32. PMID:

Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric preclinical testing program. Houghton PJ, Lock R, Carol H, Morton CL, Phelps D, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak AW, Gu Y, Wilson WR, Smith MA. Pediatr Blood Cancer. 2011 Sep;57(3):443-53. PMID: 21744473

Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program. Houghton PJ, Kang MH, Reynolds CP, Morton CL, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Maris JM, Billups CA, Smith MA. Pediatr Blood Cancer. 2012 Apr;58(4):636-9. PMID:

Combination testing (Stage 2) of the Anti-IGF-1 receptor antibody IMC-A12 with rapamycin by the pediatric preclinical testing program. Kolb EA, Gorlick R, Maris JM, Keir ST, Morton CL, Wu J, Wozniak AW, Smith MA, Houghton PJ. Pediatr Blood Cancer. 2012 May;58(5):729-35. PMID: 21630428

Initial testing of the CENP-E inhibitor GSK923295A by the pediatric preclinical testing program. Lock RB, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak AW, Gorlick R, Kolb EA, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2012 Jun;58(6):916-23. PMID: 21584937

Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program. Houghton PJ, Lock R, Carol H, Morton CL, Gorlick R, Anders Kolb E, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups CA, Zhang MX, Madden SL, Teicher BA, Smith MA. Pediatr Blood Cancer. 2012 Feb;58(2):200-9. PMID:

Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program. Morton CL, Maris JM, Keir ST, Gorlick R, Kolb EA, Billups CA, Wu J, Smith MA, Houghton PJ. Pediatr Blood Cancer. 2012 Apr;58(4):566-71. PMID: 21538824

Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. Kang MH, Reynolds CP, Houghton PJ, Alexander D, Morton CL, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Maris JM, Wozniak A, Smith MA. Pediatr Blood Cancer. 2012 Jul 15;59(1):185-8. PMID:

Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer. Carol H, Boehm I, Reynolds CP, Kang MH, Maris JM, Morton CL, Gorlick R, Kolb EA, Keir ST, Wu J, Wozniak AE, Yang Y, Manfredi M, Ecsedy J, Wang J, Neale G, Houghton PJ, Smith MA, Lock RB. Cancer Chemother Pharmacol. 2011 Nov;68(5):1291-304. PMID: 21448591

Initial testing of lenalidomide by the pediatric preclinical testing program. Reynolds CP, Kang MH, Keir ST, Gorlick R, Kolb EA, Lock R, Maris JM, Carol H, Morton CL, Billups CA, Smith MA, Houghton PJ. Pediatr Blood Cancer. 2011 Oct;57(4):606-11. PMID: 21360651

Initial testing (stage 1) of the polyamine analog PG11047 by the pediatric preclinical testing program. Smith MA, Maris JM, Lock R, Kolb EA, Gorlick R, Keir ST, Carol H, Morton CL, Reynolds CP, Kang MH, Houghton PJ. Pediatr Blood Cancer. 2011 Aug;57(2):268-74. PMID: 21360650

Initial testing (stage 1) of the mTOR kinase inhibitor AZD8055 by the pediatric preclinical testing program. Houghton PJ, Gorlick R, Kolb EA, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Phelps D, Maris JM, Billups C, Smith MA. Pediatr Blood Cancer. 2012 Feb;58(2):191-9. PMID:

Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program. Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C, Smith MA, Houghton PJ. Pediatr Blood Cancer. 2011 Apr;56(4):595-603. PMID:

Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program. Houghton PJ, Morton CL, Kang M, Reynolds CP, Billups CA, Favours E, Payne-Turner D, Tucker C, Smith MA. Pediatr Blood Cancer. 2010 Dec 1;55(6):1224-6. PMID: 20979180

National Cancer Institute pediatric preclinical testing program: model description for in vitro cytotoxicity testing. Kang MH, Smith MA, Morton CL, Keshelava N, Houghton PJ, Reynolds CP. Pediatr Blood Cancer. 2011 Feb;56(2):239-49. PMID: 20922763

Initial testing (stage 1) of AZD6244 (ARRY-142886) by the Pediatric Preclinical Testing Program. Kolb EA, Gorlick R, Houghton PJ, Morton CL, Neale G, Keir ST, Carol H, Lock R, Phelps D, Kang MH, Reynolds CP, Maris JM, Billups C, Smith MA. Pediatr Blood Cancer. 2010 Oct;55(4):668-77. PMID: 20806365

Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program. Carol H, Morton CL, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C, Smith MA, Houghton PJ, Lock RB. Pediatr Blood Cancer. 2010 Dec 15;55(7):1329-37. PMID: 20740623

Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the pediatric preclinical testing program. Keir ST, Maris JM, Lock R, Kolb EA, Gorlick R, Carol H, Morton CL, Reynolds CP, Kang MH, Watkins A, Houghton PJ, Smith MA. Pediatr Blood Cancer. 2010 Dec 1;55(6):1126-33.PMID: 20672370

Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. Morton CL, Houghton PJ, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Maris JM, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2010 Aug;55(2):295-303.. Erratum in: Pediatr Blood Cancer. 2012 Apr;58(4):652.PMID: 20582972

Initial testing of a monoclonal antibody (IMC-A12) against IGF-1R by the Pediatric Preclinical Testing Program. Houghton PJ, Morton CL, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Maris JM, Wu J, Smith MA. Pediatr Blood Cancer. 2010 Jul 1;54(7):921-6. PMID: 20166202

Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP). Maris JM, Morton CL, Gorlick R, Kolb EA, Lock R, Carol H, Keir ST, Reynolds CP, Kang MH, Wu J, Smith MA, Houghton PJ. Pediatr Blood Cancer. 2010 Jul 15;55(1):26-34. PMID: 20108338

Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric Preclinical Testing Program. Houghton PJ, Morton CL, Gorlick R, Lock RB, Carol H, Reynolds CP, Kang MH, Maris JM, Keir ST, Kolb EA, Wu J, Wozniak AW, Billups CA, Rubinstein L, Smith MA. Mol Cancer Ther. 2010 Jan;9(1):101-12. PMID: 20053767

Initial testing of topotecan by the pediatric preclinical testing program. Carol H, Houghton PJ, Morton CL, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Maris JM, Keir ST, Watkins A, Smith MA, Lock RB. Pediatr Blood Cancer. 2010 May;54(5):707-15. PMID: 20017204

Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical testing program. Smith MA, Morton CL, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Kang MH, Reynolds CP, Maris JM, Watkins AE, Houghton PJ. Pediatr Blood Cancer. 2010 Feb;54(2):307-10. PMID: 19856388

Initial testing (stage 1) of lapatinib by the pediatric preclinical testing program. Gorlick R, Kolb EA, Houghton PJ, Morton CL, Phelps D, Schaiquevich P, Stewart C, Keir ST, Lock R, Carol H, Reynolds CP, Maris JM, Wu J, Smith MA. Pediatr Blood Cancer. 2009 Oct;53(4):594-8. PMID: 19554571

Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. Carol H, Lock R, Houghton PJ, Morton CL, Kolb EA, Gorlick R, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Pediatr Blood Cancer. 2009 Dec 15;53(7):1255-63. PMID: 19554570

Initial testing (stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program. Keshelava N, Houghton PJ, Morton CL, Lock RB, Carol H, Keir ST, Maris JM, Reynolds CP, Gorlick R, Kolb EA, Wu J, Smith MA. Pediatr Blood Cancer. 2009 Sep;53(3):505-8. PMID: 19418547

Molecular characterization of the pediatric preclinical testing panel. Neale G, Su X, Morton CL, Phelps D, Gorlick R, Lock RB, Reynolds CP, Maris JM, Friedman HS, Dome J, Khoury J, Triche TJ, Seeger RC, Gilbertson R, Khan J, Smith MA, Houghton PJ. Clin Cancer Res. 2008 Jul 15;14(14):4572-83. PMID: 18628472

Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program. Keir ST, Morton CL, Billups C, Smith MA, Houghton PJ, Gururangan S. Pediatr Blood Cancer. 2008 Sep;51(3):439-41. PMID: 18493996

Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Maris JM, Courtright J, Houghton PJ, Morton CL, Kolb EA, Lock R, Tajbakhsh M, Reynolds CP, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2008 Jul;51(1):42-8. PMID: 18293383

Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program. Smith MA, Morton CL, Phelps DA, Kolb EA, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Wu J, Houghton PJ. Pediatr Blood Cancer. 2008 Jul;51(1):34-41. PMID: 18260120

Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Pediatr Blood Cancer. 2008 Jun;50(6):1190-7. PMID: 18260118

Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Lock R, Carol H, Houghton PJ, Morton CL, Kolb EA, Gorlick R, Reynolds CP, Maris JM, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2008 Jun;50(6):1181-9.PMID: 18085673

Initial testing of dasatinib by the pediatric preclinical testing program. Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock RB, Tajbakhsh M, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Pediatr Blood Cancer. 2008 Jun;50(6):1198-206.PMID: 17914733

Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Houghton PJ, Morton CL, Kolb EA, Gorlick R, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Pediatr Blood Cancer. 2008 Apr;50(4):799-805.PMID: 17635004

Initial testing of cisplatin by the pediatric preclinical testing program. Tajbakhsh M, Houghton PJ, Morton CL, Kolb EA, Gorlick R, Maris JM, Keir ST, Wu J, Reynolds CP, Smith MA, Lock RB. Pediatr Blood Cancer. 2008 May;50(5):992-1000.PMID: 17554786

Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program. Maris JM, Courtright J, Houghton PJ, Morton CL, Gorlick R, Kolb EA, Lock R, Tajbakhsh M, Reynolds CP, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2008 Mar;50(3):581-7.PMID: 17457854

Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program. Houghton PJ, Morton CL, Kolb EA, Lock R, Carol H, Reynolds CP, Keshelava N, Maris JM, Keir ST, Wu J, Smith MA. Pediatr Blood Cancer. 2008 Jan;50(1):37-45.PMID: 17420992

SK-NEP-1 and Rh1 are Ewing family tumor lines. Smith MA, Morton CL, Phelps D, Girtman K, Neale G, Houghton PJ. Pediatr Blood Cancer. 2008 Mar;50(3):703-6.PMID: 17154184

The pediatric preclinical testing program: description of models and early testing results. Houghton PJ, Morton CL, Tucker C, Payne D, Favours E, Cole C, Gorlick R, Kolb EA, Zhang W, Lock R, Carol H, Tajbakhsh M, Reynolds CP, Maris JM, Courtright J, Keir ST, Friedman HS, Stopford C, Zeidner J, Wu J, Liu T, Billups CA, Khan J, Ansher S, Zhang J, Smith MA. Pediatr Blood Cancer. 2007 Dec;49(7):928-40.PMID: 1706645