Acquired Resistance to Therapy Network (ARTNet)

Representative image for ARTNet, which focuses on the mechanistic bases of acquired resistance to cancer therapies and disease recurrence.

ARTNet (funded through RFA-CA-21-052/RFA-CA-21-053 by DCB and the NCI Division of Cancer Treatment and Diagnosis) focuses on the mechanistic bases of acquired resistance to cancer therapies and disease recurrence.

Its central goal is to balance basic, pre-clinical, and translational research using an iterative team science structure that will enable hypothesis testing on the biological basis of resistance in clinically relevant model systems.

ARTNet also aims to provide evidence along the shared tumor-tumor microenvironment (TME) continuum to inform new strategies that can be better translated into future clinical trials.

Collectively, the network represents a range of treatment modalities (e.g., chemotherapy, radiation, targeted agents, immunotherapies, combined modalities) and cancer types in pursuit of addressing compelling questions and significant barriers in acquired therapy resistance research.

ARTNet News

ARTNet Publication Highlights

Using a multi-omics approach in a study supported by ARTNet, Kirk et al. generated a mouse single-cell reference atlas for investigating prostate biology and response to cancer therapies. This resource revealed major drivers of castration-resistant prostate luminal cell populations, which may play a role in prostate cancer progression.

Researchers with the Acquired Resistance to Therapy and Iron (ARTI) Center found that inhibitors of complex I in the electron transport chain sensitize LKB1-deficient cancer cells to ferroptosis (i.e., iron-induced cell death) and radiation. They further showed that complex I inhibition synergizes with radiotherapy to suppress LKB1-deficient tumor growth in preclinical models.

Investigators with the Bay Area & Anderson Team Against Acquired Resistance (BAATAAR-UP) Center showed that a focal adhesion kinase (FAK) - YAP signaling pathway drives drug-tolerant persister cells and residual disease in lung cancer. They also found that inhibition of FAK-YAP signaling in combination with targeted therapy suppresses residual drug-tolerant cells and enhances lung tumor responses in preclinical models.

Murthy et al. with the Pancreatic Cancer ARTNet Center found that cancer-associated fibroblast-derived acetate promotes pancreatic cancer development via altering polyamine metabolism. They further showed that targeting this mechanism through inhibition of the ACSS2–SP1–SAT1 signaling pathway suppresses pancreatic cancer progression in experimental models.

ARTNet Digital Media

Learn more about ARTNet via the following digital media platforms:

DCB Contact for ARTNet

For additional information about ARTNet, please contact Dr. Jeff Hildesheim.

Funded Projects

ARTNet Research Centers (U54s)

Institution	Principal Investigator(s)	Center Title
MD Anderson Cancer Center	Boyi Gan, Albert Koong	Acquired Resistance to Therapy and Iron (ARTI) Center
MD Anderson Cancer Center	Jefferey N. Myers, Vlad C. Sandulache	The Houston Center for Acquired Resistance Research (H-CARR)
Oregon Health and Science University	Jeffery W. Tyner, Brian J. Druker, Shannon K. McSweeney	Architecture and Trajectory of Acquired Resistance to Therapy in AML
University of California, San Francisco	Trever G. Bivona, Jack Roth	Bay Area & Anderson Team Against Acquired Resistance - U54 Program (BAATAAR-UP)
University of Oklahoma Health Sciences Center	Pankaj K. Singh	Pancreatic Cancer ARTNet Center

ARTNet Coordinating and Data Management Center (U24)

Institution	Principal Investigator(s)	Center Title
Roswell Park Cancer Institute	Alan D. Hutson, David W. Goodrich, Song Liu, Martin T. Morgan	Coordinating and Data Management Center for Acquired Resistance to Therapy Network