In this study, we used previously designed Polypurine Reverse Hoogsteen (PPRH) hairpins against KRAS and MYC, either individually or as combined treatments, to decrease the expression of both oncogenes and provoke cell death in KRAS- and MYC-dependent pancreatic (AsPc-1) and prostate cancer (PC-3) cell lines. The gene discussed is KRAS; the disease is prostate cancer.