CANCER THERAPEUTICS PROGRAM - PROJECT SUMMARY/ABSTRACT Significant advances have been made in the development of novel agents and combination regimens for the treatment of human cancers. Despite this progress, major research efforts are still needed to develop new drugs to improve anticancer therapy and overcome resistance to current therapies. To achieve this goal, a close interaction between basic scientists and clinical investigators is essential to take the novel preclinical laboratory observations into the clinical setting for the treatment of human cancers. The research objectives of our MECCC Cancer Therapeutics (CT) Program have been greatly facilitated by organizing inter- and mulit-disciplinary teams of chemists, cancer biologists, cancer pharmacologists, biostatisticians and bioinformatics experts, computational biologists, and clinical investigators. The Cancer Therapeutics Program is a long-standing interdisciplinary research program. The three new Program Co-Leaders are leaders in the field of cancer therapeutics with scientific expertise that spans the entire spectrum of preclinical and clinical cancer drug development. A high priority is placed on the recruitment and mentoring of members who are deeply committed to the goals set forth by the Program and who focus on developing intra-programmatic interactions as well as strong inter-programmatic interactions/collaborations with other MECCC research programs. Significant emphasis is placed on the preclinical and clinical development of novel anticancer agents and new combination regimens for the treatment of human cancers. The overarching mission of the Program is to develop innovative approaches to discover, design, and develop novel anticancer agents and/or therapeutic regimens for the treatment of human cancers. To achieve this mission, the Program focuses on the following Specific Aims: 1). preclinical discovery and development of small molecules 2) preclinical discovery and development of biologics 3) conduct clinical trials that span early Phase I/II to late Phase III with a focus on translation of MECCC discoveries/science into investigator-initiated clinical trials, and the clinical development of novel agents in partnership with NCI-CTEP, NCI cancer centers, NCI cooperative groups, and pharmaceutical companies Notably, these specific aims align with all four of MECCC’s cross-cutting themes: 1) Bronx Catchment Area; 2) Tumor and Organ Microenvironments; 3) Prevention, Early Detection and Interception of Primary and Secondary Disease; and 4) Molecular Variations as Determinants of Outcome.