CIGB-300: A Promising Anti-Casein Kinase 2 (CK2) Peptide for Cancer Targeted Therapy

Over the past few years, the development of CK2 inhibitors using small molecules has emerged as a paradigmatic approach for blocking the enzymatic activity. However, despite successful experimental validation, so far only one of such chemical compounds has entered into clinical trials. Using a different rationale to inhibit CK2, we have developed CIGB-300 as a novel hypothesis-driven peptide targeting the CK2 phosphoacceptor domain instead of the ATP-binding site. Data from in vitro studies have revealed that at least in human cell lines from solid tumors, CIGB-300 binds mainly to and inhibits CK2-mediated phosphorylation of B23/npm. Studies of the molecular and cellular events downstream this interaction have demonstrated that CIGB-300 induces apoptosis in vitro and in vivo, modulating a wide array of proteins involved in cell proliferation, apoptosis, ribosome biogenesis, drug resistance, cell motility, and adhesion among other processes. Accordingly, CIGB-300 has shown synergistic interaction with anticancer drugs, suppressing angiogenesis and exhibiting antimetastatic properties. The pharmacology of this peptide-based drug has already been investigated in cancer patients. Different Phase 1 clinical trials have shown CIGB-300 to be safe and well tolerated and have studied its pharmacokinetics after either local or systemic administration. Remarkably, during a dose-finding Phase 2 trial in women with cervical cancer, cohorts receiving CIGB-300 and chemoradiotherapy concomitantly had a higher frequency of complete response than those receiving chemoradiotherapy alone. Taken together, the data presented here summarize all relevant preclinical and clinical findings that make CIGB-300 a promising peptide-based drug for the treatment of cancer patients.