Cancer Biology

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CANCER BIOLOGY PROGRAM: SUMMARY The Cancer Biology (CB) Program at the Hollings Cancer Center (HCC) seeks to discover the genetic and epi- genetic basis of human cancer, expose the underlying mechanisms involved in cancer initiation and progression, and develop new therapeutic strategies through statewide opportunities for treatment intervention and preven- tion. Three major themes cut across the program: 1) cancer genomics and genetics; 2) molecular regulation of gene expression; and 3) tumor micro- and macro-environment. Significant progress was made in all areas. This includes the identification of a novel stromal fibroblast signature that drives breast cancer cell proliferation; the discovery of hnRNP E1 and its target non-coding RNAs in head and neck, breast and prostate cancer; uncover- ing PLEKHA7 as a critical adherens junction component that tethers RISC to junctions and regulates RNA onco- gene expression; and the first report to identify a repressor of WNT signaling, naked cuticle homolog 1 (NKD1), as an FGF2R regulated factor that specifies hepatic cell fate. Fundamental discoveries are being translated into the clinic. For example, the identification of Advanced Glycation Endproduct (AGE) enrichment in prostate can- cer patients was developed into a phase 2 clinical trial aiming to pharmacologically reduce AGEs in breast and prostate cancer patients in an underserved community where most patients are of poor socioeconomic African American background. Thus, discoveries made in this study are being applied to understand the soci- oeconomic and environmental sources of cancer disparities and to develop tailored interventions relevant to the catchment area. The program, with 30 members from 11 departments in two colleges, is led by Philip Howe, PhD, a leader in the TGF field. CB fosters intra-, inter- and transdisciplinary research through initia- tives that have yielded extramural funding of large collaborative projects and impactful scientific discoveries. The total direct funding base for CB is $ 4.8 million (excluding career development and training grants), an increase of 60% since the prior renewal, with 14 NCI projects ($2M), 11 cancer-related grants from other NIH institutes ($1.9M), and four DOD/VAMC grants ($0.9M). CB has advanced strong collaborative research high- lighted by a strong portfolio of funded P- and U-type awards, and multi-PI R01s. Since the last review, CB members authored 122 publications, 65% of them collaborative. The exceptional impact of the program’s re- search is highlighted by significant discoveries, many with translational potential, described in top-tier journals including Cancer Cell, Mol Cell, Cell Stem Cell, Cancer Discov, Genes Dev, Nat Genet, Nat Meth, Nat Cell Biol, Nat Commun, J Clin Oncol, and J Clin Invest. With new HCC leadership, strong faculty recruitment, de- velopment of team-based interprogrammatic research and funding initiatives, and enhanced translational sci- ence infrastructure, the CB Program is poised to advance scientific discovery in all three thematic areas.