American Indians/Alaska Natives (AIAN) are disproportionately impacted by the burden of cancer. Compared to other racial and ethnic groups in the United States (US), AIAN individuals face higher rates of many cancers, later stages at diagnosis, worse outcomes after diagnosis, and lower rates of cancer survival. The Partnership for Native American Cancer Prevention (NACP), a 21-year collaboration between Northern Arizona University (NAU) and the University of Arizona Cancer Center (UACC), has made impactful strides that successfully address the causal factors that drive AIAN cancer inequities. NACP has had a significant positive impact on the pipeline of AIAN individuals seeking careers related to cancer health research, including the training of Native investigators poised to be leaders in this field. NACP has been a driver of institutional change at both NAU and UACC by fostering an increase in cancer research capacity at NAU and health disparity-focused research at UACC and by elevating both institutions’ commitments to serving AIAN students and communities. NACP has built a strong foundation of relationships with tribal communities, governments, and other partners, based on trust and respect, and this is resulting in an acceleration of the positive impacts driven by NACP’s activities, both present and future. NACP is poised to realize past investments while sustaining current relationships and expanding interactions to additional tribal communities in Arizona. The NACP remains committed to its core goals of reducing the burden of cancer within AIAN populations through research and community engagement, growing the number of AIAN investigators participating in the cancer research workforce, and increasing the total number of investigators focused on cancer health disparities within Native Arizona communities. While these overall goals remain consistent, NACP is introducing an operational framework to systematically incorporate Indigenous perspectives as a core reference to guide and thread together its work. NACP will embrace the ‘two-eyed seeing’ paradigm, which seeks to “see from one eye with the strengths of Indigenous knowledges and ways of knowing, and from the other eye with the strengths of Western knowledges and ways of knowing, and to use both of these eyes together for the benefit of all.” Aim 1. To engage in bidirectional communication grounded in the principle of reciprocity with our AIAN community partners to promote best practices with respect to cancer health and to develop research priorities and programs that address AI cancer health disparities. Aim 2. To grow the pipeline of cancer-focused Indigenous researchers and health care professionals through educational and training programs tailored to high school, undergraduates, graduate students, junior investigators, and early-stage investigators. Aim 3. Conduct impactful cancer disparity focused research that is informed by and inclusive of tribal community priorities and concer...