The Preclinical Therapeutics Grants Branch (PTGB) supports preclinical research in discovery, development, and evaluation of agents that treat human cancers. These anti-cancer agents include small molecules of either synthetic or natural product origin, peptides, antisense oligonucleotides, and siRNAs/miRNAs. Studies focused on drug design and screening are supported, up to, but not including clinical trials. Drug targets of potential anti-cancer agents include components of the tumor microenvironment (excluding applications within the ImmunoOncology Branch that focus on specific targeting of immune cells), components of signaling pathways or cellular networks; any of which are hypothesized to have oncological roles in tumor proliferation, oncogenesis and metastasis. Studies may involve biochemical, cell-based, in vivo animal models (non-mammalian and mammalian), organoids, human tissue specimens, New Approach Methodologies (NAMs); or any proposed studies useful for empirical confirmation of preclinical observations.
Major areas of study supported by PTGB include, but are not limited to:
• small molecule anti-cancer drug discovery, chemical optimization and characterization.
• small-molecule targeting or modulation of oncogenic and tumor suppressor pathways, including antibody-drug conjugates, and nanotechnology-based drugs.
• identification and validation of new therapeutic targets.
• mechanism(s) of action for new or existing drugs that lead to improved therapeutic efficacy, or treatment regimens, inclusive of drug combination strategies.
• mechanism(s) of resistance to anti-cancer agents, and identification of strategies to overcome resistance or mitigate treatment-associated toxicities.
• mechanism(s) of efficacy and toxicity for cancer drugs, with an emphasis on the roles of underlying biological systems as characterized by studies of pharmacokinetics, pharmacodynamics, pharmacogenomics, pharmacogenetics, proteomics and metabolomics.
• applications of modern machine learning and artificial intelligence approaches for extracting cancer-relevant actionable insights from derived data.
PTGB staff work at the nexus of the external grantee and research communities, and the internal Developmental Therapeutics Program (DTP) and the Division of Cancer Treatment and Diagnosis (DCTD), where non-grant resources for drug discovery and development are available. These include access to the NCI drug and natural product repositories, the NCI patient-derived models repository, the NCI60 cell line screening data, and consultation services.