Colorectal cancer (CRC) is the third most commonly diagnosed cancer and is the third leading cause of cancer-related deaths in the western world. The mortality from colorectal cancer in Caucasian American (CAs) has been declining, but the death rate continues to be higher in African Americans (AAs), maintaining the racial disparity. In addition, AAs more often present with CRC at advanced stages contributing to the lower five year survival rate. Hispanic-Americans (HAs) have significantly lower CRC incidence and mortality rates when compared with Non- Hispanic AA (NH-AA) and Non-Hispanic CA (NH- CA) populations. However, rates among HAs are significantly higher than those among residents of Puerto Rico and other Spanish-speaking countries in South and Central America. Furthermore, preliminary data and documented results show that for HA the age at presentation is lower and the stage of the disease is higher than that of AA and CAs. We hypothesize that various factors (i.e., familial, socioeconomic, environmental and dietary) may contribute to the underlying problem of colon cancer racial/ethnic health disparity. Also, it has been noted that the response to chemopreventive agents differ as to the biological/genetic heterogeneity of the tumors of NH-AAs, HAs and NH-CAs. Since chemopreventive agents exert their effect through a molecular target, this disparity would suggest differences at the genetic level. Therefore, the formulation and evaluation of chemopreventive/chemotherapeutic agents that address the issue of differential chemoresponse and chemoresistance is essential to survival. To study, in vitro and in vivo, the development of and chemo-responsiveness of therapeutic agents to colonic diseases in diverse populations, the availability of the appropriate cells (cell lines/organoids) and animal (PDX) models are critical. Our overarching goal is to assess racial and ethnic genetic/epigenetic dysregulations and associate these changes to chemoresponse and colon cancer racial disparity. The availability of these biological tools will facilitate overcoming differential incidence and outcome seen among racial and ethnic groups for CRC. To achieve this goal, we are generating and characterizing novel cell lines, PDXs and organoids derived from NH-CAs, HAs and AAs patients with colorectal cancer. Downstream use of these biological tools will assist our group and the scientific community at large in improving targeted personal cancer treatment. This research effort is inclusive of all and will benefit a diverse population.