Developmental Cancer Therapeutics Program ABSTRACT The Developmental Cancer Therapeutics (DCT) Program has evolved considerably since 2012 with an increased focus on both solid tumor oncology and the translational aspects of advancing basic science into early-phase clinical trials in rapid fashion. Under the leadership of David Horne, PhD and Edward Newman, PhD, the central theme and overarching goal of DCT are the in-house development of novel, molecularly targeted therapies and drug delivery systems for intractable cancers. Although DCT has continued the Program's long- standing strength in evaluating cancer therapeutics developed through industry partnerships, the emphasis of the DCT Program is to advance important basic discoveries made at the City of Hope Cancer Comprehensive Center (COHCCC). To this end, DCT has established clear scientific goals that fall under three central themes: 1) Support target-directed drug development by identifying and validating new molecular cancer targets/pathways and developing corresponding pharmacological agents; 2) Develop novel drug delivery platforms to improve specificity and efficacy of clinical outcomes; and 3) Translate basic discovery and preclinical studies into early-phase clinical trials. The DCT program extends across eight departments and encompasses a total of 29 Members, of which 12 are basic researchers and 17 are clinicians/clinician scientists. Through the Program, close intra- and inter-programmatic collaborations are fostered among basic scientists and clinical investigators, which in turn has yielded an increase in the number of COH-initiated agents currently under clinical investigation. During the previous grant period, significant infrastructure has been established for the creation of a strong translational research program with greater focus on solid tumor oncology, resulting in a continuous flow of new therapeutic approaches poised for early-phase clinical trials. The emphasis is on speed and precision medicine. With only GLP toxicity studies and some formulation work contracted outside, the DCT Program can rapidly translate discoveries to the clinic. This Program has been further enhanced by the strategic recruitment of key faculty (Chen, Fakih, Fong, Gold, and Salgia), implementation of a drug discovery pipeline, and cGMP manufacturing capability for small molecule drugs, such as COH29, through COH?s in-house Chemical cGMP Synthesis Facility. During the next funding period, we anticipate robust translation of our new therapeutic approaches from the discovery phase to first-in-human clinical trials and continued close collaboration with other regional and national Comprehensive Cancer Centers. Membership: 29 Program Members representing 8 basic and clinical departments Publications: 503 total. 20.1% intra-programmatic; 36.4% inter-programmatic; 41.2% inter-institutional Funding: $4,751,305 peer-reviewed; $1,794,235 of which is NCI funding

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA033572-35
Application #
9491634
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2018-04-20
Budget End
2018-11-30
Support Year
35
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Beckman Research Institute/City of Hope
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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Zhang, Bin; Nguyen, Le Xuan Truong; Li, Ling et al. (2018) Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia. Nat Med 24:450-462
Kirschbaum, Mark H; Frankel, Paul; Synold, Timothy W et al. (2018) A phase II study of vascular endothelial growth factor trap (Aflibercept, NSC 724770) in patients with myelodysplastic syndrome: a California Cancer Consortium Study. Br J Haematol 180:445-448
Moreira, Dayson; Adamus, Tomasz; Zhao, Xingli et al. (2018) STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers. Clin Cancer Res 24:5948-5962
Liu, Liang; Yang, Lin; Yan, Wei et al. (2018) Chemotherapy Induces Breast Cancer Stemness in Association with Dysregulated Monocytosis. Clin Cancer Res 24:2370-2382
Woyach, Jennifer A; Ruppert, Amy S; Heerema, Nyla A et al. (2018) Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med 379:2517-2528
Wolfson, Julie A; Richman, Joshua S; Sun, Can-Lan et al. (2018) Causes of Inferior Outcome in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: Across Oncology Services and Regardless of Clinical Trial Enrollment. Cancer Epidemiol Biomarkers Prev 27:1133-1141
Choi, Audrey H; O'Leary, Michael P; Chaurasiya, Shyambabu et al. (2018) Novel chimeric parapoxvirus CF189 as an oncolytic immunotherapy in triple-negative breast cancer. Surgery 163:336-342
Golfetto, Ottavia; Wakefield, Devin L; Cacao, Eliedonna E et al. (2018) A Platform To Enhance Quantitative Single Molecule Localization Microscopy. J Am Chem Soc 140:12785-12797
Aldoss, Ibrahim; Stiller, Tracey; Tsai, Ni-Chun et al. (2018) Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients. Haematologica 103:1662-1668

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