Development and Cancer
To conduct studies at the intersection of developmental biology and cancer biology using cell-based models and whole organisms.
The Development and Cancer Program explores the role of aberrant development in the genesis of cancer. The Program includes both laboratory researchers and physician-scientists, and features 40 members from 17 departments, including scientists from the fields of cancer, stem cell, and developmental biology. Program members investigate the developmentally and evolutionarily conserved ancestral themes that are fundamental to cell and organism growth, development, and physiology, and how these factors influence cancer biology.
- Tumor-stroma interactions
- Cancer cell programming
- Epigenetics and cell fate
- Stem cell biology
Imaging the glioma biomarker 2HG. Research spearheaded by Development and Cancer (and involving collaborations across the Cancer Center) has revealed that the metabolite 2-hydroxyglutarate (2HG), which accumulates in gliomas as a result of mutations in the genes IDH1 and IDH2, is detectable with magnetic resonance spectroscopy. The finding represents a novel example of a noninvasive imaging biomarker directly linked to a genetic mutation in a cancer cell. In a phase I/II clinical trial at UT Southwestern of a first-in-class IDH2 inhibitor, the approach is being used to provide a direct readout of IDH inhibition.
- Selected citation: Choi, C. et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 18, 624-629 (2012).
Molecularly targeted therapy for soft-tissue sarcoma. A $6.9 million grant from the Cancer Prevention and Research Institute of Texas is fueling a multi-investigator, multi-institution research project to conduct molecular genetics and functional genomics studies in soft-tissue and Ewing sarcoma. The project aims to uncover unknown drivers of soft-tissue sarcoma, with the goal of developing molecularly targeted therapies. The effort includes a biospecimen banking initiative encompassing patients at cancer centers across Texas, and builds upon UT Southwestern research developing unique, non-mammalian models of human cancer, including a Drosophila (fruit fly) model of rhabdomyosarcoma, and zebrafish models of malignant germ cell tumor and Ewing sarcoma.
- Selected citation: Leacock, S.W. et al. A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. Dis Model Mech 5, 95-106 (2012).
To Get Involved
The Program welcomes additional physicians and scientists seeking a broader and deeper understanding of how developmental processes go awry to contribute to cancer development or progression.
Topics of interest include, but are not limited to, stem cell biology, and mechanisms of lineage commitment and cellular differentiation; heterotypic cell-cell interactions in tissue/organ formation and tumor-stroma interactions; immunobiology and therapeutics of human cancer; cellular metabolism and development; and transcriptional and post-transcriptional control of gene and protein synthesis.
Contact Dr. Skapek for more details about the Development and Cancer Program, meetings, and more. firstname.lastname@example.org
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Chen, W. et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature 539, 112-117 (2016).
Choi, C. et al. Prospective longitudinal analysis of 2-hydroxyglutarate magnetic resonance spectroscopy identifies broad clinical utility for the management of patients with IDH-mutant glioma. J Clin Oncol 34, 4030-9 (2016).
DeNicola, G.M. et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet 47, 1475-81 (2015).
Guo, Y. et al. Comprehensive ex vivo transposon mutagenesis identifies genes that promote growth factor independence and leukemogenesis. Cancer Res 76, 773-86 (2016).
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Ma, G. et al. Regulation of smoothened trafficking and Hedgehog signaling by the SUMO pathway. Dev Cell 39, 438-451 (2016).
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