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Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program.

Publication ,  Journal Article
Gorlick, R; Kolb, EA; Keir, ST; Maris, JM; Lock, RB; Carol, H; Reynolds, CP; Kang, MH; Billups, CA; Collins, J; Kurmashev, D; Kurmasheva, RT ...
Published in: Pediatr Blood Cancer
March 2016

BACKGROUND: NSC 750854 is a purine analog with an antitumor activity profile distinctive from that of other anticancer purines. It has shown significant activity against adult cancer preclinical models. PROCEDURE: NSC 750854 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10 μM and against the PPTP in vivo xenograft panels administered intraperitoneally at a dose of 5 mg/kg daily for 5 days repeated at day 15. RESULTS: The median relative IC50 (rIC50 ) value for the PPTP cell lines was 32 nM (range from 11 to 124 nM), with consistent cytotoxicity across all cell lines. Acute lymphoblastic leukemia (ALL) cell lines were more sensitive to NSC 750854 than non-ALL cell lines. NSC 750854 induced significant differences in EFS distribution compared to control in 31 of 35 (89%) solid tumor xenografts. It induced tumor growth inhibition meeting criteria for intermediate or high event free survival (EFS) T/C activity in 17 of 32 (53%) evaluable solid tumor xenografts (most consistently in the rhabdomyosarcoma panel). Objective responses were observed in 15 of 37 (41%) solid tumor xenografts and in all eight leukemia models with complete response (CR) or maintained complete response (MCR) in seven of eight leukemia models. CONCLUSIONS: NSC 750854 has a unique spectrum of antitumor activity compared with other agents tested by the PPTP as it induces regression in tumor models with limited sensitivity to most agents tested to date. Given the promising level of activity observed for NSC 750854 against PPTP preclinical models, further exploration of its mechanism of action is warranted.

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Published In

Pediatr Blood Cancer

DOI

EISSN

1545-5017

Publication Date

March 2016

Volume

63

Issue

3

Start / End Page

443 / 450

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Purine Nucleosides
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oncology & Carcinogenesis
  • Mice
  • Cell Line, Tumor
  • Animals
  • 3213 Paediatrics
  • 3211 Oncology and carcinogenesis
  • 1114 Paediatrics and Reproductive Medicine
 

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Gorlick, R., Kolb, E. A., Keir, S. T., Maris, J. M., Lock, R. B., Carol, H., … Smith, M. A. (2016). Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer, 63(3), 443–450. https://doi.org/10.1002/pbc.25826
Gorlick, Richard, E Anders Kolb, Stephen T. Keir, John M. Maris, Richard B. Lock, Hernan Carol, C Patrick Reynolds, et al. “Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program.Pediatr Blood Cancer 63, no. 3 (March 2016): 443–50. https://doi.org/10.1002/pbc.25826.
Gorlick R, Kolb EA, Keir ST, Maris JM, Lock RB, Carol H, et al. Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2016 Mar;63(3):443–50.
Gorlick, Richard, et al. “Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program.Pediatr Blood Cancer, vol. 63, no. 3, Mar. 2016, pp. 443–50. Pubmed, doi:10.1002/pbc.25826.
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. Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2016 Mar;63(3):443–450.
Journal cover image

Published In

Pediatr Blood Cancer

DOI

EISSN

1545-5017

Publication Date

March 2016

Volume

63

Issue

3

Start / End Page

443 / 450

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Purine Nucleosides
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oncology & Carcinogenesis
  • Mice
  • Cell Line, Tumor
  • Animals
  • 3213 Paediatrics
  • 3211 Oncology and carcinogenesis
  • 1114 Paediatrics and Reproductive Medicine