Summary/Aims of the Supplement Project The supplement grant is to request the support for Mr. Emanuel Baltrip, a graduate student of African American, to pursue his Ph.D. training. In research aspect, he will work on his dissertation project, a part of the parent funded parent project (1R01CA257842-01A1) on developing polymeric micelle delivery of paclitaxel and cyclopamine for the treatment of hepatocellular adenocarcinoma (HCC) in orthotopic mouse models. In mentoring and career development aspect, Mr. Baltrip will be trained in developing research skills in hypothesis development, experimental study planning and execution, critical data analysis, and verbal and written communication skills, as well as developing proposals, to acquire a comprehensive set of skills for becoming a conscientious and capable cancer researcher of the underrepresented ethnicity, to fulfill the unmet clinical need for improving the survival and quality of life of HCC patients. The 3 specific aims for Mr. Baltrip’s project are: (a) De-risking of M-CPA/PTX in single- and multiple-dose toxicity to evaluate the differential toxicity in male and female mice, recently observed in Dr. Chow’s lab with male mice being more sensitive for adverse events than the female counter part. The differential drug metabolism between sexes is the hypothesis to be tested. (b) 1. Comprehensive characterization of pharmacokinetic (PK), exposure in tumor and organ biodistribution of CPA and PTX from the dose of M-CPA/PTX 2. Establishment of the dose proportionality of the unique delivery system, M-CPA/PTX after single and multiple doses that will contribute to the rational dose finding based on the established dose linearity range, and (c) Derivation of PK/pharmacodynamics (PD) correlation of M-CPA/PTX for the treatment of HCC in orthotopic mouse models, using alpha-fetoprotein as a PD biomarker for the development and treatment response of HCC to monitor the treatment efficacy of M-CPA/PTX. Other tumor measures including tumor growth suppression and animal survival will also be monitored for other PK/PD correlations. These studies will offer projection of effective exposures in plasma and tumor for the intended efficacy.