Journal
SEMINARS IN ONCOLOGY
Volume 45, Issue 1-2, Pages 58-67Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.seminoncol.2018.04.006
Keywords
CIGB-300; casein kinase 2; CK2 inhibitors; targeted therapy; anticancer peptides; cervical cancer
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Funding
- C.I.G.B.
- Biorec
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Protein kinase CK2, formerly referred to as casein kinase II, is a serine/threonine kinase often found overexpressed in solid tumors and hematologic malignancies that phosphorylates many substrates integral to the hallmarks of cancer. CK2 has emerged as a viable oncology target having been experimentally validated with different kinase inhibitors, including small molecule ATP-competitors, synthetic peptides, and antisense oligonucleotides. To date only two CK2 inhibitors, CIGB-300 and CX-4945, have entered the clinic in phase 1-2 trials. This review provides information on CIGB-300, a cell-permeable cyclic peptide that inhibits CK2-mediated phosphorylation by targeting the substrate phosphoacceptor domain. We review data that support the concept of CK2 as an anticancer target, address the mechanism of action, and summarize preclinical studies showing antiangiogenic and antimetastatic effects as well as synergism with anticancer drugs in preclinical models. We also summarize early clinical research (phase 1/2 trials) of CIGB-300 in cervical cancer, including data in combination with chemoradiotherapy. The clinical data demonstrate the safety, tolerability, and clinical effects of intratumoral injections of CIGB-300 and provide the foundation for future phase 3 clinical trials in locally advanced cervical cancer in combination with standard chemoradiotherapy. (C) 2018 Elsevier Inc. All rights reserved.
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