ABSTRACT The goal of the Developmental Therapeutics (DT) program is to translate basic scientific discovery to clinical application to benefit patients of all ages, improving the quality of life for patients in the catchment area and beyond. Members develop, test, and institute novel therapies in adult and pediatric patients with solid and hematologic malignancies and lead collaborative, multi-institutional initiatives to establish new treatment paradigms. The DT program serves the catchment area by improving access to care, and training the next generation of cancer researchers, focusing on mentoring early-career faculty. The DT program had two added points of focus as a result of the prior review: 1) enhancing investigator-initiated trials (IITs) by developing the IIT incubator and prioritizing IITs in early-phase trial and disease-specific groups, particularly those developed by mentored members. As a result, accruals to intervention treatment IITs increased 3-fold from 47 in 2016 to 140 in 2020. And 2) enhancing preclinical xenograft development to foster immunobiology/immunotherapy discovery. DT funded pilot grants producing orphan disease PDXs, humanized models (HM) for colorectal cancer, and an autologous HM in melanoma. With 78 members representing 18 departments and 4 schools, DT holds $3.2M in NCI, $2.0M in other NIH, and $2.8M in other peer-reviewed funding, a 50% increase in peer- reviewed research funding from $5.4M in 2016 to $8.0M in 2020. Since 2016, DT members enrolled 2688 subjects to 641 intervention treatment trials, an increase of 29%. DT members published 1000 peer-reviewed cancer-related papers, of which 48% were collaborative (15% inter-; 17% intra-; 16% both) and 24% in journals with an IF>10. Forty-seven percent (47%) of these represent collaborations with other NCI-designated cancer centers. University of Colorado Cancer Center (UCCC) educational activities, training/career enhancement activities, and shared resources (SRs) support are foundational to the DT's priorities of funding pilot grants that emphasize “homegrown” therapies and bench-to-bedside application of discoveries. These investments led to successful program project collaborations and multiple-PI funding across the UCCC. DT continues to expand multi-stakeholder partnerships within UCCC and with key partners, including the University of Colorado Boulder (UCB), Colorado State University (CSU), University of Colorado Hospital (UCH), Children's Hospital Colorado (CHCO), and the Veterans Administration (VA). UCH, CHCO, and the VA utilize a unified and shared Institutional Review Board, enabling a robust and compliant system to apply DT program discoveries and benefit patients in the catchment area, while streamlining access for patients. The DT program continues to focus on advancing novel compounds developed within UCCC by supporting pilot projects, using the NIH Research Evaluation and Commercialization Hubs (REACH) program, suppor...