The overall goal of the Sidney Kimmel Comprehensive Cancer Center (SKCCC) Cancer Chemical and Structural Biology (CCSB) Program is to: 1) discover, validate and characterize novel molecular targets for developing new therapeutic agents against human cancers; 2) identify new small molecules with anticancer potential and optimize their potency; and 3) improve the delivery of existing and promising new therapeutic agents. To accomplish these goals, the Program comprises faculty members across the university (e.g., the medical school, the Whiting School of Engineering and Homewood). CCSB fosters major interactions among SKCCC members and includes 22 Program members from nearly a dozen departments. Eighteen members have peer-reviewed support, with NCI and other peer-reviewed support of Program members totaling more than $10.7 million total costs and all Program support totaling $11.6 million. The productivity of CCSB members is demonstrated by the 611 publications, of which 43 (7%) were Intra-Programmatic, 144 (24%) were Inter- Programmatic and 202 (33%) were multi-institutional collaborations. Activities for the next project period stand to focus on three complementary aims:
Aim 1 : Characterize both new and existing targets using biophysical and chemical approaches.
Aim 2 : Develop small-molecule screening methods and optimize novel lead compounds for cancer targets.
Aim 3 : Develop methods for assessing and optimizing the delivery of anticancer drugs. The first goal describes predominantly laboratory-based efforts, with a focus on identifying and validating preclinical targets, and on ?proof of principle? experiments needed for further clinical testing. These activities include molecular, structural and cell biology studies, coupled with cellular and whole-animal assays, and preclinical pharmacokinetic and dynamic analyses. The second goal involves developing new chemical libraries and carrying out small-molecule screening and optimization against CCSB targets. The third goal centers on developing new methods for small-molecule delivery, including pro-drugs, encapsulation methods and delivery assessment in vivo. Through these goals, the Program will provide new preclinical candidates, along with the biology of the respective molecular targets, to investigators in other SKCCC Programs to move them further along the clinical development path. This will have a broad and powerful impact by assisting clinical researchers with basic science investigations essential to the treatment of cancer and by driving the discovery and delivery of new anticancer drugs to the clinic for real-world testing.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA006973-55
Application #
9519889
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
55
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Wei, Ting; Najmi, Saman M; Liu, Hester et al. (2018) Small-Molecule Targeting of RNA Polymerase I Activates a Conserved Transcription Elongation Checkpoint. Cell Rep 23:404-414
Kasamon, Yvette L; Fuchs, Ephraim J; Zahurak, Marianna et al. (2018) Shortened-Duration Tacrolimus after Nonmyeloablative, HLA-Haploidentical Bone Marrow Transplantation. Biol Blood Marrow Transplant 24:1022-1028
Wang, Yuxuan; Li, Lu; Douville, Christopher et al. (2018) Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med 10:
Walter, Vonn; Du, Ying; Danilova, Ludmila et al. (2018) MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors. Cancer Res 78:3375-3385
Cohen, Joshua D; Li, Lu; Wang, Yuxuan et al. (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359:926-930
Tie, Jeanne; Cohen, Joshua D; Wang, Yuxuan et al. (2018) Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut :
Stein-O'Brien, Genevieve; Kagohara, Luciane T; Li, Sijia et al. (2018) Integrated time course omics analysis distinguishes immediate therapeutic response from acquired resistance. Genome Med 10:37
Dean, Lorraine T; Montgomery, Madeline C; Raifman, Julia et al. (2018) The Affordability of Providing Sexually Transmitted Disease Services at a Safety-net Clinic. Am J Prev Med 54:552-558
Bastos, Diogo A; Antonarakis, Emmanuel S (2018) AR-V7 and treatment selection in advanced prostate cancer: are we there yet? Precis Cancer Med 1:
Lu, Dai-Yin; Yalçin, Hulya; Yalçin, Fatih et al. (2018) Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy. Am J Cardiol 121:1081-1089

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