About the network

The Cancer Immunoprevention Network (CIP-Net), established by the National Cancer Institute (NCI), is designed to advance the understanding of fundamental immunoprevention mechanisms, discover novel strategies, and support the preclinical development and testing of new interventions. It brings together a collaborative community of researchers focused on preventing cancer before it develops. Through a milestone-driven UG3/UH3 phased structure, CIP-Net enables de novo discovery of immune pathways, targets, and mechanisms, as well as the evaluation of the efficacy and potential side effects of novel interventions and immunomodulatory agents.
 

The Cancer Immunoprevention Network (CIP-Net) was established with the overarching goal of advancing a deeper understanding of the basic mechanisms that underpin cancer immunoprevention. By fostering a collaborative community of researchers, CIP-Net seeks to accelerate the discovery of innovative strategies to prevent cancer before it develops.

CIP-Net addresses an emerging need to complement ongoing and recent immunoprevention clinical trials in both humans and dogs by creating a robust pipeline of discovery science. Through its focus on fundamental research, the network is positioned to generate the mechanistic insights necessary to inform the next generation of cancer immunoprevention strategies and move closer to the goal of intercepting cancer at its earliest stages.
Cancer death rates in the U.S. continue to decline, reflecting advances in treatment, risk reduction through lifestyle changes, timely screening, and primary immunoprevention against cancers caused by infectious agents like HBV and HPV. However, about 85% of cancers are not linked to infections, and developing safe, effective interventions for these cancers remains a major challenge.

Recent preclinical studies show that immune-based interventions can successfully prevent tumor initiation and progression in animal models, supporting the potential for cancer immunoprevention in at-risk human populations. Preventive interventions offer distinct advantages by stimulating strong immune responses in healthy individuals before cancer-related immune suppression occurs.

Tumorigenesis is a dynamic process shaped by interactions between emerging abnormal cells and host immune surveillance. Understanding how early immune pathways either suppress or promote tumor growth is critical. Factors such as chronic inflammation and tissue injury can lead to immune dysfunction, while precancerous lesions may have more favorable microenvironments for immune targeting. Key questions remain about when immune targets arise during cancer development and how best to stimulate protective immunity.

Emerging genomic and molecular profiling data from NCI initiatives like The Human Tumor Atlas Network (HTAN), Pre-Cancer Atlas (PCA), Translational and Basic Science Research in Early Lesions (TBEL), and Molecular and Cellular Characterization of Screen-detected Lesions (MCL) provide opportunities to identify novel immune pathways, targets, and adjuvants. These insights can guide the design of interventions, using preclinical models that mimic high-risk cohorts, ultimately driving progress toward effective cancer immunoprevention beyond infection-driven cancers.
U24 Data and Resource Coordinating Center (DRCC):
The U24 DRCC serves as a central hub to enhance data and resource sharing, as well as collaborations within CIP-Net. It provides bioinformatics and analytical support, drives scientific communications and meetings to raise awareness, and conducts outreach to engage both complementary cancer research communities and the lay public. In addition, the DRCC is dedicated to fostering the growth and development of early career scientists in cancer immunoprevention.

UG3/UH3 Research Projects:
The UG3/UH3 research projects aim to advance cancer immunoprevention through a two-phase approach. The UG3 phase focuses on discovering and exploring novel immune pathways, mechanisms, and innovative targets for immunopreventive interventions. Progress is evaluated through milestone-driven reviews by NCI staff. Successful projects transition to the UH3 phase, which emphasizes validation, deeper mechanistic studies, and preclinical testing to assess pathways, efficacy, and potential side effects.
In the UG3 phase, research focuses on de novo discovery of immune pathways, elucidating mechanisms of immunoprevention, and conducting preclinical investigations of new interventions, immunomodulatory targets, or agents with potential for future clinical development. This phase emphasizes early-stage innovation, with clearly defined, quantifiable milestones that include objective go/no-go criteria to track progress.

Successful achievement of these milestones is required for transition to the UH3 phase , where projects advance to deeper evaluation of efficacy, mechanisms of action, and validation of actionable targets. This phase may also involve further preclinical development to refine interventions and assess safety.

This structured, stepwise approach ensures rigorous evaluation and efficient advancement of promising immunoprevention strategies from discovery toward potential clinical impact.
  • Cancer immunoprevention: Cancer immunoprevention is the prevention of invasive cancer onset (not recurrence) with immunological means such as immunomodulatory agents.
  • Cancer interception: Cancer interception is defined as the disruption of the oncogenic process during the precancer stage before the development of invasive cancer (not recurrence).
  • Higher-risk populations, higher-risk cohorts: These are individuals with an increased risk of cancer such as those with hereditary cancer syndromes (HCS) and precursor abnormalities that place individuals at higher risk of cancer, e.g., precancer.
  • Precision cancer prevention and interception: Precision cancer prevention-interception refers to an approach employing cancer preventive-interceptive interventions individually tailored for different higher-risk populations as defined above.
CIP-Net is supported by both the NCI Division of Cancer Biology and the NCI Division of Cancer Prevention.