Molecular Oncology Program

University Of California, San Francisco, San Francisco CA

Investigators

Linked publications, trials & patents

Abstract

Experimental Therapeutics Program: Summary The overarching mission of the Experimental Therapeutics (ET) Program is to discover and validate therapeutic targets and subsequently identify, develop, and test novel therapeutic strategies and biomarkers. The close collaboration between discovery scientists and clinicians allows a multifaceted assessment of therapeutic strategies in iterative cycles from bench to bedside. Discoveries within the rich scientific environment of the HDFCCC have resulted in the development of a large number of biotech start-ups, and the movement of discoveries into the private sector for clinical implementation. Most often, this takes the form of early biotech start-ups launched by UCSF faculty. Thus, this discovery cycle can also include `bench to boardroom,' since the lengthy arc from initial discovery to clinical approval and adoption requires industrial participation ranging from early biotech start-ups to pharmaceutical companies. Genomic and molecular imaging target validation are a central clinical focus of the ET Program. Promising clinical translational strategies are tested in the HDFCCC Early Phase Clinical Trials Unit. In addition to facilitating translation of science from its members, the ET Program serves as a clinical translational hub for the entire HDFCCC, since all clinical investigators in the ET Program participate in disease-specific Site Committees. These investigators consequently serve as a two-way conduit of collaborative interactions between the Site Committees and the ET Program. Research in the ET Program is conducted under two cross-cutting themes: Theme 1: Targeting Signal Transduction in Cancer Theme 2: Targeting Epigenetic Modulation, Cellular Homeostasis, and the Tumor Environment ET Program: Key Metrics Membership (13 departments, 2 schools) 43 Full 31 Associate 12 Cancer-relevant Funding (direct costs as of $21,511,484 05/31/2017) NCI $3,071,012 14% Peer-reviewed $3,740,309 17% Non-peer-reviewed $14,700,162 68% Cancer-relevant Publications (1/2012-7/2017) 672 Inter-programmatic 262 39% Intra-Programmatic 150 22% High-Impact 189 28% Accruals to Clinical Trials (2016) 237 63 Therapeutic 133 59 Other Interventional 0 2 Non-interventional 104 2 The MO Program aims to continue expanding its leadership role for the analysis and interpretation of genomic and genetic information. This includes working closely with cancer-specific programs, the basic science programs, and the Cancer Control Program. One key future direction is functional genomics CRISPR screens and single cell efforts. Members of the Program have developed many of the high throughput CRISPRi, CRISPRa and combined screening tools for identification of important cancer drug targets and their interactions. The availability of these tools will allow for widespread collaboration across the Cancer Center. This includes human, mouse, and primary cell screens, along with screens for genes involved with the immune recognition of cancer. This strategy is presently being integrated into the studies of systems genetics in the mouse, by using custom CRISPR guide libraries to identify the critical genes that control different stages of tumor progression. This will lead to identification of new drug targets that will be followed up by members of the MO Program to translate potential new targets into drug candidates. CRISPR screening tools will also be used to study at the singel cell level the development of drug resistance arising from acquisition of genetic and epigenetic changes. The clinical efforts of the MO Program focus on phase I trials and tissue agnostic target-based basked trials. Examples include vaccine and small molecule based clinical trials against Kras mutations. The strong collaborations established with imaging investigators, that cuts across many of the Center?s Programs including Drs. Pampaloni, VanBrocklin, Ronen (NE), and Vigneron (PR) will continue to leverage cross programmatic resources to develop molecular imaging modalities such hyperpolarized C13 and novel PET tracers in a murine models as well as in several clinical trials. Craik and Shokat received a UCSF Invent Fund technology award in January of 2020 on targeting intracellular tumor antigens with immunotherapy. The proposal brings the technologies of the two labs together to develop use human engineered antibodies to engage with MHC1-peptide complexes for therapeutic intervention. Atreya, Turnbaugh, and Goga have made considerable progress showing that bacteria are widespread in tumors, are found within cells, and differ by cancer type and are preparing their collaborative research paper for resubmission.