Incident rates of hepatocellular carcinoma (HCC) have more than doubled over the last 20 years in the United States, and no other state has felt the impact more than Texas. The rate for South Texas Hispanic/Latinos is >3 times higher than for US White non-Hispanics. Advanced HCC has an extremely poor prognosis with few therapeutic options. Sorafenib, the only available chemotherapeutic for HCC, extends median survival by only 2.8 months. Recently, 8 Phase III clinical trials with small molecule drugs have failed. These failures highlight the challenge of treating HCC, the need to develop alternative drugs including microRNAs and CRISPR/Cas, and the lack of knowledge regarding cellular spe...

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Incident rates of hepatocellular carcinoma (HCC) have more than doubled over the last 20 years in the United States, and no other state has felt the impact more than Texas. The rate for South Texas Hispanic/Latinos is >3 times higher than for US White non-Hispanics. Advanced HCC has an extremely poor prognosis with few therapeutic options. Sorafenib, the only available chemotherapeutic for HCC, extends median survival by only 2.8 months. Recently, 8 Phase III clinical trials with small molecule drugs have failed. These failures highlight the challenge of treating HCC, the need to develop alternative drugs including microRNAs and CRISPR/Cas, and the lack of knowledge regarding cellular specificity, given that the late-stage cancer environment amplifies drug and drug/gene carrier toxicity to limit efficacy. Promising RNA-based cancer treatments are currently hindered by the lack of delivery vehicles that avoid cancer-induced toxicity, a problem compounded by scarce knowledge of the optimal therapeutic timing and targets that could reverse cancer growth. We will determine the efficacy of RNA therapies that suppress the oncogenic pathways in liver cancer and understand the mechanisms of response. Results will determine the overall best approach (delivery, timing, and targets) to reverse cancer progression. Long term, the knowledge gained from completing these studies will lead to new treatment options for patients, coupled to a prescription guidance for doctors and clinicians to know how and when to give the medicine to patients with HCC.

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