Development and Cancer
Mission
To conduct studies at the intersection of developmental biology and cancer biology in living animals.
Overview
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.
Themes
- Tumor-stroma interactions
- Cancer cell programming
- Epigenetics and cell fate
- Stem cell biology
Peer-Reviewed Funding
2015 total – $33.3 million
Leadership
Stephen X. Skapek, M.D. Professor, Pediatrics
Joshua Mendell, M.D., Ph.D.
Professor, Molecular Biology
Of Note
A $6.9 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) 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.
Cancer Cell Networks
Mission
To promote research that will contribute to an understanding of the mechanisms at work in aberrant cell regulatory networks that support cancer initiation and growth.
Overview
The Cancer Cell Networks Program facilitates investigations that shed light on the mechanisms by which aberrant cell regulatory networks support the initiation of cancers. Program members’ approaches range from structural biology to animal models.
Cancer Cell Networks has 45 members representing 14 departments and centers. Key goals of the program are to define mechanisms and pathways that integrate external and internal regulatory cues at the cell-autonomous level; to determine how aberrant cell regulation contributes to the transformation of normal cells to cancer cells; and to engage translational and clinical scientists in investigating whether modulating specific aspects of cell regulation has therapeutic potential against cancer.
Themes
- Chromatin regulation
- Autophagy
- G protein signaling
- Organelle communication
- Stem cells
- RNA processing
- Inflammation
- Metabolism
Peer-Reviewed Funding
2015 total – $37.2 million
Leadership
Melanie Cobb, Ph.D.
Professor, Pharmacology
Pier Paolo Scaglioni, M.D.
Associate Professor, Internal Medicine
Of Note
Supported by new CPRIT funding of more than $889,000, Dr. Zhijian “James” Chen and colleagues are shedding light on innate immune responses to DNA and RNA. The researchers previously discovered a new enzyme, cyclic GMP-AMP synthase (cGAS), that acts as a sensor of innate immunity. The work also has described a novel cell signaling pathway: When cGAS detects foreign DNA or even host DNA that is in the cell’s cytoplasm, the enzyme binds to the DNA, catalyzing formation of a chemical called cyclic GMP-AMP, or cGAMP. Then cGAMP binds to the protein STING, activating a signaling cascade that produces interferons and pro-inflammatory cytokines. The work also has revealed a potential new avenue for enhancing anti-tumor immunity and developing cancer vaccines.
Chemistry and Cancer
Mission
To discover drug-like chemicals that impede (or enhance) biological processes related to the development (or inhibition) of cancer.
Overview
The Chemistry and Cancer Program combines the expertise of synthetic and medicinal chemists, molecular biologists, biochemists, structural biologists, and clinician-scientists to discover, design, and optimize drug-like small molecules that regulate biological pathways deregulated in cancer. The program engages 19 members drawn from six departments on campus. The program’s discovery process takes one of two approaches. For a chemistry-to-biology approach, discovery starts by identifying natural or unnatural small molecules that are selectively lethal to human cancer cell lines, then determining exactly how the small molecules have their effect. In a biology-to-chemistry approach, hypotheses regarding the “drugability” and cancer relevance of specific biological pathways investigated by Cancer Center scientists can be tested with drug-like chemicals.
Themes
- Molecular targets of cancer cell-specific small-molecule toxins
- Novel, cancer cell-specific pathways
- Proof-of-concept preclinical development of cancer cell-specific small-molecule toxins
- The hypoxia response pathway
Peer-Reviewed Funding
2015 total – $10.9 million
Leadership
Steven McKnight, Ph.D. Chair, Biochemistry
Jef De Brabander, Ph.D.
Professor, Biochemistry
John MacMillan, Ph.D.
Associate Professor, Biochemistry
Of Note
Supported by nearly $1.5 million from the National Institutes of Health, Simmons Cancer Center investigators (with collaborators at Simon Fraser University) are developing an innovative research paradigm to characterize mechanisms of action of natural products and botanicals more quickly and precisely. The approach of the new Center for High-Throughput Functional Annotation of Natural Products (HiFAN) incorporates natural products chemistry, biological screening, data analytics, and bioinformatics, combining two high-throughput platforms (cytological profiling and a technique called FuSiOn, developed at UT Southwestern) to discern in greater detail the impact on cells of both complex chemical mixtures and pure natural compounds.
Experimental Therapeutics of Cancer
Mission
To identify and validate novel targets, pathways, and therapies for selective tumor targeting; to establish biomarkers that can predict tumor response; and to test the efficacy of resulting potential medicines in clinical trials.
Overview
The Experimental Therapeutics Program supports development of novel therapeutic strategies for cancer. The program provides a science-based infrastructure for translating discoveries from the Cancer Center’s scientific programs to preclinical models and then to evaluation through investigator-initiated clinical trials.
Program leaders and members interact extensively with the Cancer Center’s disease-oriented teams to focus specific therapeutics on select cancers based on laboratory research that indicates optimal targets and relevant biomarkers.
The program represents key oncology disciplines and has 44 members, comprising 12 basic science investigators and 32 clinical investigators from 15 departments or centers. It is also home to the Cancer Center’s Specialized Program of Research Excellence (SPORE) in lung cancer.
Themes
- Molecular therapeutic sensitizers
- Tumor microenvironment and protein therapy
- Imaging and drug delivery
- Cancer vulnerabilities
Peer-Reviewed Funding
2015 total – $27 million
Leadership
John Minna, M.D.
Professor, Internal Medicine and Pharmacology
David Boothman, Ph.D.
Professor, Simmons Cancer Center
David Gerber, M.D.
Associate Professor, Internal Medicine
Of Note
Research by the lab of Dr. David A. Boothman on the anti-cancer effects of the natural substance beta-lapachone has led to two multidisciplinary projects—funded through PanCAN and totaling $1.3 million—testing the substance against pancreatic ductal adenocarcinoma (PDA) and non-small cell lung cancer (NSCLC). The first project is pursuing lab studies and a phase IB clinical trial involving chemotherapy plus a formulation of beta-lapachone called ARQ761 (from the biotechnology firms NQ Oncology and ArQule). The other project is exploring the efficacy of combining ARQ761 with PARP inhibitors to treat PDA, NSCLC, and other NQO1 over-expressed malignancies. The combination has proved effective against pancreatic, breast, and non-small cell lung cancer cells in vitro, and NSCLC in mouse xenografts.
Population Science and Cancer Control
Mission
To understand and impact factors associated with cancer risk in clinical, safety-net, and community settings among diverse populations.
Overview
Drawing from the large and diverse population that Simmons Cancer Center serves, the Population Science and Cancer Control Program has a special focus on uninsured residents served by local public health systems. Studies are centered on cancer disparities among subpopulations of individuals who traditionally are medically underserved.
Research focuses on processes of care with the goal of translating findings into improved cancer care in local health systems. The 25 members of the Population Science Program are based in five departments and at the University of Texas School of Public Health’s Dallas campus.
Themes
- Cancer prevention (including the study of biomarkers for colon and liver cancers and risk prevention behaviors)
- Screening for early detection of colon, liver, and esophageal cancers
- Cancer survivorship
Peer-Reviewed Funding
2015 total – $6.1 million
Leadership
Ethan Halm, M.D., M.P.H.
Professor, Internal Medicine
Jasmin Tiro, Ph.D., M.P.H.
Associate Professor, Clinical Sciences
Of Note
A thriving research effort is evaluating strategies to improve screening effectiveness and ensure that more people at high risk for hepatocellular carcinoma (HCC), the most common form of liver cancer, receive appropriate testing so tumors can be detected earlier and treated more effectively. Population Science program members are key investigators for the multi-institution Texas HCC Consortium, a $9.7 million initiative funded by the Cancer Prevention and Research Institute of Texas. Consortium projects include characterizing factors that predict liver cancer in a diverse group of patients with cirrhosis, evaluating novel biomarkers to increase sensitivity for early tumor detection, and a trial comparing interventions to boost screening rates in at-risk patients.
