The latest roundup of cancer research by University of Chicago experts highlights a study showing how young mothers with breast cancer often don’t follow through with needed radiation therapy, a link between inflammatory bowel disease and colorectal cancer, Ibrutinib’s work at limiting cell proliferation in chronic lymphocytic leukemia, a prognostic tool for neuroblastoma and testing bevacizumab in glioblastoma.
These members of the University of Chicago Medicine Comprehensive Cancer Center are making great advances in the understanding and treatment of cancer and their work, published in peer-reviewed scientific and medical journals, does not always get a lot of external publicity.
UChicago Cancer Conversations will be regularly highlighting the latest research with the greatest impact.
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Child care demands contribute to radiation therapy noncompliance among breast cancer patients
Despite evidence supporting the effectiveness of radiation therapy after breast-conserving surgery for young women with breast cancer, young women with children may be less likely to be compliant. To understand the factors that affect compliance in patients so they could be preemptively addressed, Ya-Chen Tina Shih, PhD, associate professor of medicine, and her colleagues analyzed data from more than 21,000 women aged 20 to 64 with breast-conserving surgery. They found that patients with at least one child aged less than seven years were significantly less likely to receive radiation therapy than their counterparts with older or no children. Other contributing factors were breast cancer quality of care measures, enrollment in health maintenance organizations or capitated preferred provider organizations, where they had to travel for breast-conserving surgery, and whether patients were primary insurance policy holders. This study underscores the importance of competing demands from child care as a barrier to complete breast cancer treatment. (Pan et al., J Natl Cancer Inst 106:djt340, 2014)
Beta-catenin signaling controls T cells and IBD-associated colorectal cancer
Signaling through the Wnt/beta-catenin pathway is upregulated in most colorectal cancers, but there are unanswered questions about the cell types in which it is acting and how it is involved in the disease. In a new study, Comprehensive Cancer Center investigator Fotini Gounari, PhD, assistant professor of medicine, found that beta-catenin is expressed in T cells in patients with inflammatory bowel disease (IBD) and colon cancer, specifically in a subset of T cells called T regulatory cells (Tregs). Gounari’s laboratory also demonstrated that Treg-specific Wnt/beta-catenin signaling was sufficient to drive the proinflammatory properties of the colon tissue and initiate tumor formation in an animal model. (Keerthivasan et al., Sci Transl Med 6:225ea28, 2014)
Click here for a news release about the study.
Ibrutinib’s anticancer activity in CLL is primarily due to blocking cell growth
Ibrutinib is a bruton agammaglobulinemia tyrosine kinase (BTK) inhibitor that has demonstrated activity in chronic lymphocytic leukemia (CLL) in early clinical trials. The research team of new Comprehensive Cancer Center member, Y. Lynn Wang, MD, PhD, professor of pathology and Director of the Genomic and Molecular Pathology Laboratory, analyzed ibrutinib’s mechanism of action in an ongoing phase Ib trial in CLL. They discovered that inhibiting cell proliferation was one of the drug’s primary effects and that signaling molecules critical for cell growth downstream of BTK were coordinately suppressed in samples from treated CLL patients over time. These data provide valuable mechanistic insights into the activity of this promising inhibitor of B cell signaling in CLL. (Cheng et al., Leukemia 28: 649-657, 2014)
Validation of a prognostic gene signature for high-risk neuroblastoma
Gene-expressing profiling has led to the development of powerful prognostic tools for several, but not all, types of cancer. A multi-institutional team led by Susan Cohn, MD, professor of pediatrics, recently described the first use of a high-throughput digital system to assess the expression of a multigene signature in high-risk neuroblastoma tumors. The researchers found that the nCounterTM 42-gene panel, but not other established prognostic factors, stratified the high-risk groups of patients into two subgroups with significantly different overall and event-free survival. These findings emphasize the prognostic value of molecular signatures in high-risk neuroblastoma patients. (Stricker etal., Mol Oncol Jan 31 Epub ahead of print, 2014)
Testing bevacizumab in newly diagnosed glioblastoma
Currently, the standard-of-care treatment for patients with newly diagnosed glioblastoma is concurrent chemotherapy (i.e., temozolomide) and radiotherapy followed by maintenance temozolomide. A multi-institutional team including Comprehensive Cancer Center member James Dignam, PhD, associate professor of health studies, examined whether bevacizumab -a biological therapy against vascular endothelial growth factor A approved for recurrent glioblastoma – would improve survival in newly diagnosed glioblastoma patients. In this randomized, double-blind, placebo-controlled clinical trial, the investigators found that there was no statistically significant improvement in overall survival. However, progression-free survival was longer in the bevacizumab group even though it did not reach the prespecified improvement target. (Gilbert et al., N Engl J Med 370:699-708)