Experimental Therapeutics is the programmatic home for basic and clinical investigators involved in a broad spectrum of studies in cancer therapeutics. The goals of the program are: (1) to develop novel agents for the treatment of cancer based upon targets identified in this and other programs, (2) to improve the activities of established classes of drugs by structural modification and/or enhanced understanding of their pharmacological properties, (3) to develop more effective clinical therapeutic regimens within the context of disease-focused working groups. Preclinical drug development continues in the areas of transition-state inhibitors, novel microtubule-stabilizing agents, and a diverse spectrum of immunotherapeutics. Two transition-state inhibitors are now in clinical trials, one advanced. A third is moving forward to the clinic. A monoclonal antibody (moab) to melanin linked to 188-rhenium completed Phase I clinical trials for the treatment of advanced melanoma. Other moab-radionuclides are being developed targeting cervical and pancreatic cancers. An agent for the prevention of the dermatitis due to EGFR inhibitors recently entered a Phase II clinical trial. The spectrum of agents studied has broadened to encompassing aptamers, high-affinity antibodies, agents to block apoptotic pathways or targeted to surface glycans. Research in biologicals is focused on co-inhibitory elements within the immune synapse with the objective of developing agents that modulate tolerance, research activities supported by the expanding capabilities in protein production, synthetic chemistry, x-ray crystallography, NMR, and mass spectroscopy with bioinformatics and systems and computational biology support. Disease-focused working groups encompassing basic and clinical investigators have been expanded in breast, gynecological, lung, and head/neck cancers and in the hematological malignancies. Neuro-oncology and neuroendocrine tumors groups were recently formed. Recruitment of clinical and translational researchers has been enhanced by a recently funded Paul Calabresi Career Development Award for Clinical Oncology Scholars. Access to patients for clinical trials has been enhanced at the affiliated Montefiore Medical Center by the creation of the multidisciplinary Montefiore-Einstein Center for Cancer Care and the recruitment of a cadre of clinician investigators. AECC members play important roles in ECOG-ATRIN, GOG, COG, and the AIDS Malignancy Consortium. There are currently 54 members from 23 departments, supported by 10 NCI grants ($2.6M Direct) and 21 other peer-reviewed cancer-relevant grants ($10.2M Direct). Since the last CCSG review there have been 537 cancer-relevant research papers by members of this program of which 29% represent intraprogrammatic, and 27% represent interprogrammatic publications.

Public Health Relevance

The goal of this program is to develop drugs that are effective in the treatment of cancer. Drugs are designed to inhibit specific target sites within cancer cells. In another approach antibodies linked to radioactive chemicals are targeted to tumor cells. Other studies are exploring the mechanisms by which tumor cells escape immune attack in order to identifying drugs that enhance the immune response to tumors. Groups of physicians focus on specific cancers to develop new therapies with anticancer drugs and radiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA013330-41
Application #
8753329
Study Section
Subcommittee B - Comprehensiveness (NCI)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
41
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
City
Bronx
State
NY
Country
United States
Zip Code
10461
Mao, Serena P H; Park, Minji; Cabrera, Ramon M et al. (2018) Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth. Breast Cancer Res 20:131
Mocholi, Enric; Dowling, Samuel D; Botbol, Yair et al. (2018) Autophagy Is a Tolerance-Avoidance Mechanism that Modulates TCR-Mediated Signaling and Cell Metabolism to Prevent Induction of T Cell Anergy. Cell Rep 24:1136-1150
Yang, Chia-Ping Huang; Wang, Changwei; Ojima, Iwao et al. (2018) Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of ?-Tubulin and the Multidrug Resistance Associated P-Glycoprotein. J Nat Prod 81:600-606
Guan, Fangxia; Tabrizian, Tahmineh; Novaj, Ardijana et al. (2018) Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis. Front Nutr 5:37
Wang, Tao; Hosgood, H Dean; Lan, Qing et al. (2018) The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies. Front Genet 9:352
Chennamadhavuni, Divya; Saavedra-Avila, Noemi Alejandra; Carreño, Leandro J et al. (2018) Dual Modifications of ?-Galactosylceramide Synergize to Promote Activation of Human Invariant Natural Killer T Cells and Stimulate Anti-tumor Immunity. Cell Chem Biol 25:571-584.e8
Limi, Saima; Senecal, Adrien; Coleman, Robert et al. (2018) Transcriptional burst fraction and size dynamics during lens fiber cell differentiation and detailed insights into the denucleation process. J Biol Chem 293:13176-13190
Rocha, Agostinho G; Franco, Antonietta; Krezel, Andrzej M et al. (2018) MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science 360:336-341
Cabahug-Zuckerman, Pamela; Stout Jr, Randy F; Majeska, Robert J et al. (2018) Potential role for a specialized ?3 integrin-based structure on osteocyte processes in bone mechanosensation. J Orthop Res 36:642-652
Vilchèze, Catherine; Copeland, Jacqueline; Keiser, Tracy L et al. (2018) Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxotrophy. MBio 9:

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