The Cancer Pharmacology (CP) Program has the overall goal to discover and develop more effective cancer treatments through pharmacology-based preclinical research. The ultimate aim is to improve patient outcomes through innovative and integrative research in cancer target biology, chemical biology, medicinal chemistry, pharmaceutics and biomedical engineering. Defining molecular functions of cancer targets and leveraging this knowledge to drive translational bench-to-bedside and bedside-to-bench research in drug discovery and delivery are signature Program features that span the Rutgers/Princeton Consortium. CP provide a platform for productive, collaborative and impactful science and discoveries. CP has 37 members from 18 Departments, 7 Schools, 2 Universities. The Program is well funded with $16.5M annual direct peer-reviewed grant support, $6.1M of which is cancer-focused (13 R01 equivalent, and 6 Multi-PI). CP members published 746 papers (up from 522 in 2004-10), 29% of which are collaborative (18% intra- and 18% inter-programmatic) with 22% in top-tier journals and 53% collaborative with other institutions. This represents an increase in both total and collaborative publications compared with last project period. Impactful science includes regulation of growth pathways by GRM1 in melanoma, novel mechanisms of amino acid signaling by mTOR in colorectal cancer, and epigenetic regulation in pediatric glioblastomas/sarcomas. CP members revealed key roles of mTOR and antioxidant pathways in cardiac protection and chronic pain management, which have implications for reducing cardiac toxicity, a dose-limiting side effect of chemo-therapy, and for improving analgesia in advanced stage cancer patients. Based on fundamental insights into the biology of molecular targets, CP members determined the mode of action for riluzole (a repurposed ALS drug) targeting GRM1 in melanoma and identified determining factors for therapeutic response for rapamycin. CP members focused on development of novel therapeutics and drug delivery technologies, and identified novel anticancer agents including a compound that restores mutant p53 function, BMI-1 inhibitors, and prodrugs for riluzole and the CINJ-developed topoisomerase 1 inhibitor Genz-644282. They developed innovative tumor-targeting nanocarriers containig multiple therapeutic modalities (small molecules, toxins, nucleic acids, and peptides/antibodies) and imaging enhancers (e.g., rare earth elements and Mn3O4), enabling cancer detection and treatment. CP members work with other CINJ Programs, particularly the Clinical Investigations and Precision Therapeutics Program (CIPT), to translate bench discoveries to clinical trials, contributing significantly to CINJ?s translational pipeline. They also use feedback from trials to gain further insight into target biology and mechanisms of treatment response for agents such as riluzole to improve therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA072720-20
Application #
9632905
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
20
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Rbhs -Cancer Institute of New Jersey
Department
Type
DUNS #
078728091
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Zhu, Sining; Jin, Juan; Gokhale, Samantha et al. (2018) Genetic Alterations of TRAF Proteins in Human Cancers. Front Immunol 9:2111
Perekatt, Ansu O; Shah, Pooja P; Cheung, Shannon et al. (2018) SMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium. Cancer Res 78:4878-4890
Llanos, Adana A M; Tsui, Jennifer; Rotter, David et al. (2018) Factors associated with high-risk human papillomavirus test utilization and infection: a population-based study of uninsured and underinsured women. BMC Womens Health 18:162
Hadigol, Mohammad; Khiabanian, Hossein (2018) MERIT reveals the impact of genomic context on sequencing error rate in ultra-deep applications. BMC Bioinformatics 19:219
Severson, Eric A; Riedlinger, Gregory M; Connelly, Caitlin F et al. (2018) Detection of clonal hematopoiesis of indeterminate potential in clinical sequencing of solid tumor specimens. Blood 131:2501-2505
Shih, Weichung Joe; Lin, Yong (2018) Relative efficiency of precision medicine designs for clinical trials with predictive biomarkers. Stat Med 37:687-709
Ding, Qiang; Gaska, Jenna M; Douam, Florian et al. (2018) Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease. Proc Natl Acad Sci U S A 115:E6310-E6318
Winer, Benjamin Y; Shirvani-Dastgerdi, Elham; Bram, Yaron et al. (2018) Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection. Sci Transl Med 10:
Modi, Parth K; Wang, Ye; Kirk, Peter S et al. (2018) The Receipt of Industry Payments is Associated With Prescribing Promoted Alpha-blockers and Overactive Bladder Medications. Urology 117:50-56
Dai, Zhuqing; Feng, Simin; Liu, Anna et al. (2018) Anti-inflammatory effects of newly synthesized ?-galacto-oligosaccharides on dextran sulfate sodium-induced colitis in C57BL/6J mice. Food Res Int 109:350-357

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