Abstract CANCollaborate is a groundbreaking initiative focused on revolutionizing rare cancer research through global cooperation and was founded upon the realization that collective action is crucial for effectively addressing the myriad rare forms of cancer. Rare cancers typically have outdated treatment guidelines, a lack of targeted therapy options due to insufficient research into their biology, and consequently, a failure to keep pace with the advancements in survival outcomes seen in more common cancers over the past few decades. The initiative is rooted in five core premises: the shared goal of all stakeholders to improve rare cancer care, the prevalence of rare cancers constituting a substantial global burden, the scattered nature of rare cancer researchers and resources, existing disincentives hindering collaboration, and the untapped potential of coordinated efforts. CANCollaborate addresses these challenges by fostering open communication, encouraging cooperation, and creating collaborations among researchers, institutions, pharmaceutical and biotech companies, patient advocacy groups, financiers, and regulators. The first focus is on appendiceal cancer (AC). AC is exceedingly rare, affecting 1 to 2 people per million, but incidence has been increasing with one study seeing a 232% increase in the U.S. between 2000 and 2016. For some subtypes of AC, management is extrapolated from colorectal cancer (CRC) guidelines, even though it was established that AC is molecularly distinct from CRC. Coordinated collaboration is essential in advancing the field, given that many physicians involved in treating and researching appendiceal cancer often have it as a secondary focus, rather than being their primary area of concentration. In our brief existence, we've successfully facilitated collaborations for appendiceal organoid generation and testing by connecting a leading organoid scientist with a physician who sees AC patients. Additionally, we have established collaborations with a biotech company with an ex-vivo drug testing platform to surgical oncologists for commencing AC susceptibility testing to potential therapeutics. Key components of CANCollaborate include regular communication, frequent workshops, promoting transparency, and sharing research developments, challenges, and results. By forming collaborations among diverse stakeholders, CANCollaborate seeks to diversify and de-risk rare cancer research by eliminating existing disincentives by rewarding collaborative efforts and fostering new forms of incentives, transforming high-risk, low-return efforts into high-return, low-risk endeavors. CANCollaborate invites all stakeholders in the field of cancer research to join by working together, sharing knowledge, and creating a global network. Together we can accelerate progress, eliminate redundancy, and ultimately contribute to the eradication of cancer. Citation Format: Jamie Barber, Kyra Itskowitz, Jane Wilkinson. CANCollaborate: Transforming rare cancer research through cooperation and collaboration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB088.