Houghton Lab

Dr. Houghton and staff

Peter Houghton, PhD

Rank: Professor
Department: Molecular Medicine
Office: 2.110.12
Tel: 210.562.9056

Our studies aim to understand the mechanisms of cancer initiation in children and use this information to develop more effective and less toxic treatments that will increase the cure rate and improve the quality of life for cancer survivors.

UTHSA Faculty Profile: Peter J. Houghton,, PhD

Lab Research

Research Project A

Childhood Glioma

The most common brain tumor in children is astrocytoma. These tumors can occur in any part of the brain and are derived from astrocytes, a type of glial cell that provides nutrition to neurons in the brain. Astrocytoma may occur as familial cancer or as sporadic cancer. There is an increased risk of low-grade astrocytoma with a genetic condition called neurofibromatosis 1 (NF1). These familial astrocytomas are associated with mutations in the NF1 gene that encodes a negative regulator of RAS, leading to constitutive signaling through the MAP kinase and PI3 kinase pathways and continued cell proliferation. Sporadic low-grade astrocytoma, often referred to as Juvenile Pilocytic Astrocytoma (JPA), is also associated with the activation of the MAP kinase signaling pathway. These tumors are indolent (slow-growing) and well-circumscribed without invasion into surrounding brain tissue. Genomic studies have shown that ~90% of these low-grade tumors have a tandem duplication involving the KIAA1549 and BRAF genes that generate constitutively active KIAA1549::BRAF fusions. Higher-grade tumors tend to have activating point mutations of BRAF, most frequently the V600E variant. Such activating mutations are identified in diffuse astrocytomas (23%), gangliogliomas (33%), and pleomorphic xanthoastrocytoma (70%). Some 10-15% of pediatric glioblastomas and many epithelioid glioblastomas also carry this mutation. Drawing from available databases (ACS and CBTRUS), approximately 1400 new pediatric BRAF mutant brain tumors and 350 adult brain tumors are diagnosed annually.

We identified a drug that inhibits a kinase (MEK) downstream in the signaling cascade and causes the arrest of proliferation and death of these cancer cells. Selumetinib has recently completed phase I and II testing through the Pediatric Brain Tumor Consortium (PBTC) and Children’s Oncology Group (COG). Selumetinib shows promising activity. This project builds upon our initial work to develop effective therapies that prevent or retard the emergence of drug-resistant cells and to explore the therapeutic value of combining selumetinib (or other MEK inhibitors) with radiation therapy.

More on Project A 

Research Project B

The Pediatric In Vivo Testing Program (PIVOT)

The PPTC builds upon fifteen years of testing 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 100 drugs, or drug combinations, have been tested in approximately 100 models of childhood cancer (kidney cancers, sarcomas, neuroblastoma, liver cancers, brain cancers, and acute lymphoblastic leukemia.) These studies have identified novel drugs and drug combinations that are now in a clinical trial.

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Research Project C

Signaling Pathways in Childhood Sarcoma

Our earlier studies have identified insulin-like growth factor (IGF) signaling as maintaining the proliferation of sarcoma cells and being involved in angiogenesis by regulating vascular endothelial cell response to VEGF. The current studies, supported through a Program Project Grant from NCI, aim to identify resistance mechanisms to therapeutics that target the IGF-axis. These studies integrate IGF, STAT3, and NFκB signaling pathways in childhood sarcoma models both in vitro and in vivo.

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Research Project D

The CPRIT Texas Pediatric Testing Program

Through the combined efforts of Drs. Houghton, Kurmasheva, and Zheng at GCCRI, with support from the Cancer Prevention and Research Institute of Texas (CPRIT, Texas Pediatric Patient Derived Xenograft Facility, RP160716), we have generated approximately 160 new models of pediatric cancers. The list of CPRIT-derived solid tumor and leukemia PDX models are shown in Tables 1 and 2.

More on Project D


Review Articles

  • 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
  • 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
  • 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: 0.3389/fonc.2015.00193. eCollection 2015. Review.PMID:26380223
  • Targeting FANCD2 for therapy sensitization. Shen C, Houghton PJ.Oncotarget. 2014 Jun 15;5(11):3426-7. No abstract available. PMID:24913333
  • Rhabdomyosarcoma: current challenges and their implications for developing therapies. Hettmer S, Li Z, Billin AN, Barr FG, Cornelison DD, Ehrlich AR, Guttridge DC, Hayes-Jordan A, Helman LJ, Houghton PJ, Khan J, Langenau DM, Linardic CM, Pal R, Partridge TA, Pavlath GK, Rota R, Schäfer BW, Shipley J, Stillman B, Wexler LH, Wagers AJ, Keller C. Cold Spring Harb Perspect Med. 2014 Nov 3;4(11):a025650. doi: 10.1101/cshperspect.a025650. Review.PMID: 25368019
  • Drug discovery in pediatric oncology: roadblocks to progress. Adamson PC, Houghton PJ, Perilongo G, Pritchard-Jones K.Nat Rev Clin Oncol. 2014 Dec;11(12):732-9. doi: 10.1038/nrclinonc.2014.149. Epub 2014 Sep 16. Review.PMID:25223555
  • Targeting FANCD2 for therapy sensitization. Shen C, Houghton PJ.Oncotarget. 2014 Jun 15;5(11):3426-7. No abstract available. PMID:24913333
  • Regulation of mammalian target of rapamycin complex 1 (mTORC1) by hypoxia: causes and consequences. Cam H, Houghton PJ. Target Oncol. 2011 Jun;6(2):95-102. doi: 10.1007/s11523-011-0173-x. Epub 2011 Apr 16. Review.PMID: 21499767
  • Targeting angiogenesis in childhood sarcomas. Bid HK, Houghton PJ. Sarcoma. 2011;2011:601514. doi: 10.1155/2011/601514. Epub 2010 Dec 9. PMID: 21197468, Everolimus. Houghton PJ. Clin Cancer Res. 2010 Mar 1;16(5):1368-72. doi: 10.1158/1078-0432.CCR-09-1314. Epub 2010 Feb 23. Review.PMID: 20179227

Recent Publications: