Cancer Biology Program (CBP)

癌症生物学程序：摘要

CANCER BIOLOGY PROGRAM: ABSTRACT The overarching scientific goal of the Cancer Biology Program (CBP) at the University of Arizona Cancer Center (UACC) is to understand the basic biological processes that underlie cancer etiology and progression. Our goal is to use the knowledge we generate on these processes to identify new therapeutic targets and biomarkers and to establish interprogrammatic collaborations to bring them to the clinic. The Specific Aims of CBP are to: (1) elucidate the basic mechanisms that control tumor-relevant cell growth and proliferation; (2) identify etiologic mechanisms in cancer initiation and progression; and (3) determine how the tumor microenvironment influences progression, invasion, and metastasis. CBP is comprised of 52 Members in 16 departments and five colleges. CBP Members have made a significant impact on basic cancer mechanisms as evidenced by being the first to: (1) identify a quiescence switch in dormant cells; (2) find a link between fumarate hydratase and ferroptosis in kidney cancer; (3) demonstrate centrosome loss as a major driver of prostate cancer initiation; (4) decipher the underlying functional defects in cancer-specific Polβ mutations; (5) identify a role for TDP-43 in DNA repair and stress granules; (6) identify a link between the androgen receptor (AR) and integrin α6β1 in metastatic castration-resistant prostate cancer; (7) find a role for estrogen receptor in suppressing mechanical-driven invasion in breast cancer; and (8) decipher how Helicobacter pylori evades the immune system to initiate gastric cancer. Through interprogrammatic collaborations and hand-offs to the Clinical & Translational Oncology Program, CBP Members are translating their findings by designing new drugs to target the androgen receptor and glycogen synthetase kinase in prostate and colon cancer, respectively; testing new Fe+ chelating agents in kidney cancer; designing peptides to target EGFR and integrin α6β1 in breast and prostate cancer, respectively; evaluating miR130b as a new biomarker for gastric cancer; using organoid/immune cell co-cultures to design personalized combination therapies for pancreatic cancer; and testing cannabinoid receptor agonists to overcome bone pain in breast cancer patients. UACC provided support to CBP through funding of pilot awards and coordination of programmatic meetings, seminars, retreats, and workshops that foster intra- and interprogrammatic collaborations and transdisciplinary translational research. These meetings supported strategic recruitment of 17 new faculty since 2016. CBP has a peer-review funding base of $9.8M (direct costs) of which $2M (20%) is from the National Cancer Institute, $7.2M (73%) from other National Institutes of Health sources, and $0.6M (6%) from other peer-reviewed sources. This represents a 49% increase in peer-reviewed funding over the previous project period. During the current project period, Members authored 386 cancer-relevant publications, of which 46 (12%) were intraprogrammatic, 78 (20%) were interprogrammatic, and 187 (48%) were inter-institutional. In addition, CBP Members filed 29 patents, of which two were issued, and mentored over 50 trainees.