San Diego was a picture-perfect backdrop for the 105th Annual Meeting of the American Association of Cancer Research (AACR) on April 5-9, 2014.
More than 18,000 attendees, including cancer researchers, patient advocates and other professionals from the cancer field around the globe, gathered to share the latest basic, translational and clinical cancer research discoveries.
The theme for this year’s meeting, “Harnessing Breakthroughs – Targeting Cures”, reflects the commitment among the cancer research community to advance research findings from the laboratory bench to the cancer patient’s bedside with an accelerated pace and personalized approach.
The University of Chicago Medicine Comprehensive Cancer Center’s presence was felt at the conference from start to finish, from exciting sessions led by our investigators to numerous posters presented by trainees and countless visitors to our booth in the Exhibit Hall. In sum, leading-edge research from 40 Comprehensive Cancer Center members representing 10 different departments was presented at the meeting.
Here are some selected highlights:
Lucy Godley, MD, PhD, associate professor of medicine, chaired a Methods Workshop on “Beyond DNA Methylation and Histone Acetylation” that provided practical information on the latest techniques in epigenetic research.
Her talk detailed experimental approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine at the genome-wide scale and at single-base resolution. Describing methodologies that have been largely developed by collaborator and fellow UCCCC member Chuan He, PhD, professor of medicine, Dr. Godley also highlighted the successful application of these innovative technologies to her work over the last several years, specifically in characterizing the epigenetic changes associated with erythropoiesis and hematological malignancies.
In a Meet-the-Expert session, Mark Ratain, MD, Leon O. Jacobson Professor of Medicine, discussed the strategies and challenges of cancer pharmacogenomics. Because germline variation can greatly influence a patients’ response to the effectiveness and toxicity of drug treatments, understanding this variation has the potential to guide the use of anticancer therapies.
Dr. Ratain presented some of the methodological challenges associated with cancer pharmacogenomics, including genotyping, phenotyping and statistical analyses. He also provided some examples of the insights gained by implementing these approaches as well as important perspective about the opportunities ahead for the pharmacogenomics field.
Ken Onel, MD, PhD, associate professor of pediatrics, chaired and presented his latest work in a session on “Radiation and Breast Cancer: Linking Genetics, Epidemiology, and Biology.”
He described recent work from his group in which a genome-wide association study identified variants in the PRDM1 gene associated with therapy-induced second malignancies. These variants comprise a risk locus associated with decreased basal expression of PRDM1 protein and impaired induction of PRDM1 after radiation exposure.
More recent unpublished functional and bioinformatic studies have revealed the pathway by which radiation activates PRDM1, as well as the downstream consequences of the risk locus on PRDM1-mediated tumor suppression. The significance of this work lies in the fact that it reveals a genetic susceptibility locus that, in the absence of radiation does not affect cancer risk, but which, in the presence of radiation, increases risk for cancer form 3% to 30%.
In a Minisymposium on “Novel Small Molecules and Targets”, recent data from a collaborative project from the laboratories of Wendy Stock, MD, professor of medicine, and Yusuke Nakamura, MD, PhD, professor of medicine, were presented by Houda Alachkar, PharmD, PhD, a Clinical Pharmacology and Pharmacogenomics fellow.
She described the group’s preclinical studies of a MELK kinase inhibitor in acute myeloid leukemia (AML) and found that MELK inhibition resulted in significant cytoxicity in AML cell line and primary blasts.
Other Minisymposia presentations featured collaborations involving Jianjun Chen, PhD, assistant professor of medicine, on microRNA-mediated leukemia-initiating cell activity, and Olufunmilayo Olopade, MBBS, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, and Dezheng Huo, MD, PhD, assistant professor of health studies, identifying breast cancer risk loci in African-American women.
In addition to these presentations, Eileen Dolan, PhD, professor of medicine, and Olopade served as roundtable mentors in a professional advancement session, the 17th Annual Grant Writing Workshop, organized by the Associate Member Council.
For many that attend the AACR annual meeting, the lively, well-attended poster sessions are the highlight. And the more than 54 presentations from the Comprehensive Cancer Center did not disappoint.
Although space limitations preclude us from sharing highlights of all of the distinguished work presented, there were multiple posters presented from the Nakamura laboratory and collaborators, including identification of recurrent somatic mutations in muscle-invasive bladder cancer (with Gary Steinberg, MD, Bruce and Beth White Family Professor of Surgery, and Peter O’Donnell, MD, assistant professor of medicine), and T cell receptor repertoire analysis in non-small cell lung cancer and graft vs. host disease patients (the latter from a collaboration with Michael Bishop, MD, professor of medicine, Amittha Wickrema, PhD, associate professor of medicine, and Andrew Artz, MD, assistant professor of medicine).
Graduate and MD, PhD students from the laboratory of Kay Macleod, PhD, associate professor of the Ben May Department for Cancer Research, presented several posters describing their work characterizing how autophagy influences tumor progression, the modification of autophagy as a therapeutic strategy for head and neck squamous cell carcinoma, and the role of BNIP3 in tumor development through effects on metabolism and mitophagy.
Projects from the Olopade group were presented on the aberrant expression of ribosomal protein p1 in breast cancer, basal-like breast cancer-specific methylation patterns of miR-29c, and analysis of the MELK gene amplification and copy number alterations in endometrial, ovarian, and breast cancer cell lines (the latter in a collaborative project with the Nakamura laboratory).
Other collaborative projects presented as posters included: the derivation of bone trophic human prostate cancer cells by Carrie Rinker-Schaeffer, PhD, professor of surgery, and Russell Szmulewitz, MD, assistant professor of medicine; evaluation of poly(ADP-ribose) polymerase inhibitor efficacy in head and neck cancer by Tanguy Seiwert, MD, assistant professor of medicine, Ralph Weichselbaum, MD, D.K. Ludwig Professor of Radiation and Cellular Oncology, and Everett Vokes, MD, John E. Ultmann Professor of Medicine; role of gene body cytosine modifications in O(6)-methylguanine-DNA methyltransferase (MGMT) gene expression and sensitivity to temozolomide from Drs. Godley and Dolan; and the prediction of clinical drug responses using gene expression levels and in vitro drug sensitivity by Stephanie Huang, PhD, assistant professor of medicine, and Nancy Cox, PhD, professor of medicine.